RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

PURPOSE: To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. RESULTS: The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. CONCLUSION: A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

Targeting ferroptosis: a novel insight against myocardial infarction and ischemia-reperfusion injuries.

Ferroptosis, a newly discovered form of regulated cell death dependent on iron and reactive oxygen species, is mainly characterized by mitochondrial shrinkage, increased density of bilayer membranes and the accumulation of lipid peroxidation, causing membrane lipid peroxidation and eventually cell death. Similar with the most forms of regulated cell death, ferroptosis also participated in the pathological metabolism of myocardial infarction and myocardial ischemia/reperfusion injuries, which are still the leading causes of death worldwide. Given the crucial roles ferroptosis played in cardiovascular diseases, such as myocardial infarction and myocardial ischemia/reperfusion injuries, it is considerable to delve into the molecular mechanisms of ferroptosis contributing to the progress of cardiovascular diseases, which might offer the potential role of ferroptosis as a targeted treatment for a wide range of cardiovascular diseases. This review systematically summarizes the process and regulatory metabolisms of ferroptosis, discusses the relationship between ferroptosis and myocardial infarction as well as myocardial ischemia/reperfusion injuries, which might potentially provide novel insights for the pathological metabolism and original ideas for the prevention as well as treatment targeting ferroptosis of cardiovascular diseases such as myocardial infarction and myocardial ischemia/reperfusion injuries.

Soluble RAGE attenuates myocardial I/R injuries via FoxO3-Bnip3 pathway.

Soluble receptor for advanced glycation end-products (sRAGE) was reported to inhibit cardiac apoptosis through the mitochondrial pathway during myocardial ischemia/reperfusion (I/R) injury. Meanwhile, the proapoptotic protein Bcl2 and adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) was reported to mediate mitochondrial depolarization and be activated by the Forkhead box protein O3 (FoxO3a). Therefore, it is supposed that FoxO3a-Bnip3 pathway might be involved in the inhibiting effects of sRAGE on mitochondrial apoptosis during I/R. I/R surgery or glucose deprivation/reoxygenation was adopted to explore mitochondrial depolarization, apoptosis and related signaling pathways in mice hearts and cultured cardiomyocytes. The results showed that overexpression of sRAGE in cardiomyocytes dramatically improved cardiac function and reduced infarct areas in I/R treated mice. sRAGE inhibited mitochondrial depolarization and cardiac apoptosis during I/R, which correlated with reduced expression of Bnip3, Sirt2, phosphorylation of Akt and FoxO3a which translocated into nucleus in cultured cardiomyocytes. Either Sirt2 or FoxO3a silencing enhanced the inhibiting effects of sRAGE on mitochondrial depolarization induced by I/R in cultured cardiomyocytes. Meanwhile, overexpression or silencing of FoxO3a affected the inhibiting effects of sRAGE on Bnip3 and cleaved caspase-3 in cultured cardiomyocytes. Therefore, it is suggested that sRAGE inhibited I/R injuries via reducing mitochondrial apoptosis through the FoxO3a-Bnip3 pathway.

Diagnosis, Treatment, and Management for Chronic Coronary Syndrome: A Systematic Review of Clinical Practice Guidelines and Consensus Statements.

Objectives: Management of chronic coronary syndrome (CCS) encompasses a broad spectrum of practices, posing considerable complexity and variability. While guidelines have been established to augment the management quality of CCS, notable disparities persist across their recommendations. This study strives to scrutinize, compare, and reconcile these guideline recommendations pertaining to the diagnosis, treatment, and management of CCS patients. Our goal is to align these recommendations with contemporary clinical practices, thus laying a robust foundation for their pragmatic application in clinical settings. Methods: A comprehensive systematic search was conducted across multiple databases, including PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, Chinese Biomedical Literature Service System, Chinese Science and Technology Periodical Database, and Chinese Biological Medicine Database. The timeframe for this search spanned from their inception up to May 30, 2022, aiming to collate all published guidelines relevant to CCS. Subsequently, two independent reviewers undertook the task of appraising the quality of these guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation II instrument. Results: The search yielded a total of 10,699 citations. Following a thorough evaluation, fourteen clinical practice guidelines and four consensus statements, each offering specific recommendations for CCS, were selected. The quality of these guidelines showcased a broad spectrum of variation. The domain of "presentation clarity" received the highest accolades, while "applicability" languished at the lower end of the scoring spectrum. On average, the guidelines attained a quality score denoting sufficiency. Furthermore, recommendations across different guidelines for the diagnosis, treatment, and management of CCS displayed a striking level of divergence. Conclusion: The landscape of published CCS guidelines is marked by extensive variations in scope, quality, and recommendations. Hence, there is a compelling need for collaborative efforts amongst multidisciplinary professionals to forge comprehensive, higher-quality evidence-based guidelines; such a concerted approach is paramount to enhance treatment efficacy and health outcomes for patients grappling with CCS.

Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters.

Mixed-lineage leukemia 1 (MLL1) introduces 1-, 2- and 3-methylation into histone H3K4 through the evolutionarily conserved set domain. In this study, bovine embryonic stem cells (bESCs, known as bESCs-F7) were established from in vitro-fertilized (IVF) embryos via Wnt signaling inhibition; however, their contribution to the endoderm in vivo is limited. To improve the quality of bESCs, MM-102, an inhibitor of MLL1, was applied to the culture. The results showed that MLL1 inhibition along with GSK3 and MAP2K inhibition (3i) at the embryonic stage did not affect bESCs' establishment and pluripotency. MLL1 inhibition improved the pluripotency and differentiation potential of bESCs via the up-regulation of stem cell signaling pathways such as PI3K-Akt and WNT. MLL1 inhibition decreased H3K4me1 modification at the promoters and altered the distribution of DNA methylation in bESCs. In summary, MLL1 inhibition gives bESCs better pluripotency, and its application may provide high-quality pluripotent stem cells for domestic animals.

SD-RLK28 positively regulates pollen hydration on stigmas as a PCP-Bß receptor in Arabidopsis thaliana.

Pollen hydration on dry stigmas is strictly regulated by pollen-stigma interactions in Brassicaceae. Although several related molecular events have been described, the molecular mechanism underlying pollen hydration remains elusive. Multiple B-class pollen coat proteins (PCP-Bs) are involved in pollen hydration. Here, by analyzing the interactions of two PCP-Bs with three Arabidopsis thaliana stigmas strongly expressing S-domain receptor kinase (SD-RLK), we determined that SD-RLK28 directly interacts with PCP-Bß. We investigated pollen hydration, pollen germination, pollen tube growth, and stigma receptivity in the sd-rlk28 and pcp-bß mutants. PCP-Bß acts in the pollen to regulate pollen hydration on stigmas. Loss of SD-RLK28 had no effect on pollen viability, and sd-rlk28 plants had normal life cycles without obvious defects. However, pollen hydration on sd-rlk28 stigmas was impaired and pollen tube growth in sd-rlk28 pistils was delayed. The defect in pollen hydration on sd-rlk28 stigmas was independent of changes in reactive oxygen species levels in stigmas. These results indicate that SD-RLK28 functions in the stigma as a PCP-Bß receptor to positively regulate pollen hydration on dry stigmas.

Integrinß3 mediates the protective effects of soluble receptor for advanced glycation end-products during myocardial ischemia/reperfusion through AKT/STAT3 signaling pathway.

Soluble receptor for advanced glycation end-product (sRAGE) was reported to protect myocardial ischemia/reperfusion (I/R) injuries via directly interacting with cardiomyocytes besides competing with RAGE for AGEs. However, the specific molecule for the interaction between sRAGE and cardiomyocytes are not clearly defined. Integrins which were reported to interact with RAGE on leukocytes were also expressed on myocardial cells, therefore it was supposed that sRAGE might interact with integrins on cardiomyocytes to protect hearts from ischemia/reperfusion injuries. The results showed that sRAGE increased the expression of integrinß3 but not integrinß1, ß2, ß4 or ß5 in cardiomyocytes during I/R injuries. Meanwhile, the suppressive effects of sRAGE on cardiac function, cardiac infraction size and apoptosis in mice were cancelled by inhibition of integrinß3 with cilengitide (CLG, 75 mg/kg). The results from cultured cardiomyocytes also proved that sRAGE attenuated myocardial apoptosis and autophagy through interacting with integrinß3 to activate Akt and STAT3 pathway during oxygen and glucose deprivation/reperfusion (OGD/R) treatment. Furthermore, the phosphorylation of STAT3 was significantly downregulated by the inhibition of Akt (LY294002, 10 µM) in OGD/R and sRAGE treated cardiomyocytes, which suggested that STAT3 pathway was induced by Akt in I/R and sRAGE treated cardiomyocytes. The present study contributes to the understanding of myocardial I/R pathogenesis and provided a novel integrinß3-dependent therapy strategy for sRAGE ameliorating I/R injuries.

Atrial myocyte-derived exosomal microRNA contributes to atrial fibrosis in atrial fibrillation.

BACKGROUND: Atrial fibrosis plays a critical role in the development of atrial fibrillation (AF). Exosomes are a promising cell-free therapeutic approach for the treatment of AF. The purposes of this study were to explore the mechanisms by which exosomes derived from atrial myocytes regulate atrial remodeling and to determine whether their manipulation facilitates the therapeutic modulation of potential fibrotic abnormalities during AF. METHODS: We isolated exosomes from atrial myocytes and patient serum, and microRNA (miRNA) sequencing was used to analyze exosomal miRNAs in exosomes derived from atrial myocytes and patient serum. mRNA sequencing and bioinformatics analyses corroborated the key genes that were direct targets of miR-210-3p. RESULTS: The miRNA sequencing analysis identified that miR-210-3p expression was significantly increased in exosomes from tachypacing atrial myocytes and serum from patients with AF. In vitro, the miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis in atrial fibroblasts. Accordingly, miR-210-3p knock out (KO) reduced the incidence of AF and ameliorated atrial fibrosis induced by Ang II. The mRNA sequencing analysis and dual-luciferase reporter assay showed that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is a potential target gene of miR-210-3p. The functional analysis suggested that GPD1L regulated atrial fibrosis via the PI3K/AKT signaling pathway. In addition, silencing GPD1L in atrial fibroblasts induced cell proliferation, and these effects were reversed by a PI3K inhibitor (LY294002). CONCLUSIONS: Atrial myocyte-derived exosomal miR-210-3p promoted cell proliferation and collagen synthesis by inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may be a novel target to ameliorate atrial fibrosis in patients with AF.

Bacteroides fragilis prevents aging-related atrial fibrillation in rats via regulatory T cells-mediated regulation of inflammation.

BACKGROUND: Aging plays a critical role in the genesis of atrial fibrillation (AF) and also changes the gut microbes. Whether the aging-associated gut dysbiosis contributes to the development of aging-related AF and whether the gut microbes can be a target to prevent aging-related AF remains unknown. METHODS AND RESULTS: 16S rRNA gene sequencing was performed to reveal the changes of gut microbes in elderly patients with AF, and the result showed that the intestinal abundance of B. fragilis was significantly decreased in elderly patients with AF. Subsequently, we examined the impact of B. fragilis supplementation on AF promotion, atrial structural remodeling and inflammation response in D-galactose induced aging rats. We found that oral administration of B. fragilis prevented AF inducibility and duration, which was associated with attenuation of atrial senescence, apoptosis and fibrosis. Furthermore, B. fragilis significantly diminished the systemic and atrial inflammation, which is accompanied by an increase in the number of Treg cells in the spleen and blood. More importantly, we found that the circulation level of polysaccharide A (PSA), the metabolite synthesized by B. fragilis, was reduced in elderly patients with AF and could predict the occurrence of AF, and B. fragilis increased the circulation concentration of PSA in D-galactose induced aging rats. CONCLUSIONS: The abundance of B. fragilis was lower in elderly patients with AF. Oral administration of B. fragilis significantly attenuated inflammatory response by increasing Treg cells, thereby preventing atrial structural remodeling and inhibiting AF promotion in D-galactose induced aging rats. This study provides experimental evidence for the effectiveness of targeting gut microbes in the prevention of aging-related AF.

Effects of ticagrelor monotherapy vs. clopidogrel monotherapy on platelet reactivity: a randomized, crossover clinical study (SINGLE study).

Increasing clinical trials demonstrated that the discontinuation of aspirin while maintaining a P2Y12 inhibitor monotherapy could decrease the risk of bleeding without losing the antithrombotic effect. However, no data are available on the platelet reactivity of patients undergoing ticagrelor monotherapy vs. clopidogrel. Therefore, we performed this study to observe the efficacy of ticagrelor monotherapy vs. clopidogrel in Chinese patients with chronic coronary syndrome. This randomized, single-blinded, crossover trial enrolled 50 patients who were administered with ticagrelor (90 mg twice daily for 2 weeks) or clopidogrel (75 mg once daily for 2 weeks). Followed by a 2-week washout period, the two groups of patients underwent a crossover trial. Light transmission aggregometry (LTA) and thromboelastography (TEG) assays were used to test platelet reactivity. The platelet aggregation rate (PAgR) of ADP and AA was significantly lower with ticagrelor than clopidogrel (PAgR of ADP, 27.30% (7.30%-42.635%) vs. 35.55% (12.03%-69.25%), P = .0254; PAgR of AA, 77.80% (21.60%-86.43%) vs. 83.10% (67.13%-87.20%), P = .0400). There was no significant difference in PAgR of collagen and epinephrine between the two groups. The TEG assay showed that ADP and AA, which induced the inhibition of platelet aggregation, were significantly higher in the ticagrelor group than those in the clopidogrel group [ADP%, 69.00% (59.68%-88.95%) vs. 60.55% (35.98%-78.35%), P = .0020; AA%, 53.65% (22.75%-79.28%) vs. 15.15% (5.75%-70.25%), P = .0127]. High on-treatment platelet reactivity (HTPR) on ADP was 2.17% with ticagrelor and 19.57% with clopidogrel. HTPR on AA was 50.00% with ticagrelor and 69.57% with clopidogrel. Ticagrelor and clopidogrel caused the inhibition of ADP and AA-induced platelet aggregation. Moreover, ticagrelor monotherapy had a stronger inhibitory effect than clopidogrel monotherapy (except on collagen and epinephrine).

Soluble receptor for advanced glycation end-products promotes angiogenesis through activation of STAT3 in myocardial ischemia/reperfusion injury.

Soluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis remains unclear. Myocardial model of I/R injury was conducted by left anterior descending (LAD) ligation for 30 min and reperfusion for 2 weeks in C57BL/6 mice. And I/R injury in cardiac microvascular endothelial cells (CMECs) was duplicated by oxygen and glucose deprivation. The results showed that I/R-induced cardiac dysfunction, inflammation and myocardial fibrosis were all reversed by sRAGE. CD31 immunohistochemistry staining showed that sRAGE increased the density of vessels after I/R injury. The results from cultured CMECs showed that sRAGE inhibited apoptosis and increased proliferation, migration, angiogenesis after exposure to I/R. These effects were dependent on signal transducer and activator of transcription 3 (STAT3) pathway. Together, the present study demonstrated that activation of STAT3 contributed to the protective effects of sRAGE on myocardial I/R injury via promoting angiogenesis.

Atorvastatin Attenuates Cold-Induced Hypertension by Preventing Gut Barrier Injury.

Chronic exposure to cold causes arterial hypertension [cold-induce hypertension (CIH)]. Emerging data have indicated that gut barrier dysfunction is involved in the pathogenesis of hypertension. In this study, we explored the effect of gut barrier dysfunction on vascular inflammation induced by cold exposure and the therapeutic effect of atorvastatin in a CIH rat model. The CIH was established by cold exposure for 2 weeks. Two groups of Sprague Dawley rats were exposed to moderate cold (4 ± 1°C), whereas the control group was maintained at room temperature (23 ± 1°C) (10 rats/group). The 2 groups received atorvastatin or vehicle at the beginning of cold exposure, respectively, for 2 weeks. Cold exposure increased mean arterial pressure compared with room temperature group, indicating that animals developed arterial hypertension. Cold exposure induced vascular dysfunction due to decreasing phosphorylated endothelial nitric oxide synthase protein expression in aorta, and these were blunted by atorvastatin. Cold exposure increased the levels of gut-derived inflammatory cytokines, tumor necrosis factor-α, and interleukin-6 production in aorta and resulted in vascular inflammation, whereas atorvastatin prevented these effects. Cold exposure also increased gut permeability, inhibited tight junction protein expression in proximal colon, and resulted in gut barrier dysfunction. Interestingly, atorvastatin eliminated increasing gut permeability, decreasing tight junction protein expression, and gut pathology and reversed gut barrier dysfunction. Atorvastatin attenuated CIH and improved gut barrier function; the beneficial effects might be via inhibiting gut-derived inflammatory cytokines and reversing cold-induced vascular inflammation, suggesting that gut barrier dysfunction may be involved in the pathogenesis of CIH.

Ticagrelor protects against AngII-induced endothelial dysfunction by alleviating endoplasmic reticulum stress.

Ticagrelor has been reported to decrease cardiovascular mortality compared with clopidogrel. This benefit cannot be fully explained by the more efficient platelet inhibition. Many studies demonstrated that ticagrelor improved endothelial function, leaving the mechanism elusive though. The present study aims to investigate whether ticagrelor protects against endothelial dysfunction induced by angiotensinII (AngII) through alleviating endoplasmic reticulum (ER) stress. Male Sprague Dawley rats were infused with AngII or vehicle and administrated with ticagrelor or vehicle for 14 days. Reactive oxygen species (ROS) was detected. Aortas from normal mice were incubated with endoplasmic reticulum stress inducer tunicamycin with or without ticagrelor. Vasorecactivity was measured on wire myography. Rat aortic endothelial cells (RAECs) were pretreated with ticagrelor followed by AngII or tunicamycin. Endothelial nitric oxide synthase (eNOS) phosphorylation and ER stress markers were determined by western blotting. Impaired endothelial function, induction of ER stress, reduced eNOS phosphorylation and elevated ROS generation was restored by ticagrelor treatment in vivo. In addition, tunicamycin induced endothelial dysfunction was improved by ticagrelor. In vitro, the induction of ER stress and inhibited eNOS phosphorylation in REACs exposed to AngII as well as tunicamycin was reversed by co-culturing with ticagrelor. In conclusion, ticagrelor protects against AngII-induced endothelial dysfunction via alleviating ER stress.

Relaxin alleviates TGFß1-induced cardiac fibrosis via inhibition of Stat3-dependent autophagy.

Cardiac fibrosis is a pathological feature common to a variety of heart diseases such as myocardial infarction, arrhythmias, cardiomyopathies and heart failure. Emerging data has indicted that autophagy is involved in fibrotic synthesis. Relaxin as a pleiotropic hormone can attenuate cardiac fibrosis and hypertrophy, however the exact molecular mechanism remains largely unknown. In this work, we evaluated whether the antifibrotic effect of relaxin relies on regulating autophagy in primary cardiac fibroblasts (CFs). Our results showed that relaxin significantly attenuated TGFß1-induced autophagy in parallel with the reduction of fibrosis. Moreover, relaxin inhibited the phosphorylation of Stat3/Smad3 signaling. Then we observed that knockdown of Stat3 synchronously suppressed the fibrogenesis and autophagic flux which was stimulated by TGFß1 in CFs. More importantly, we simultaneously administrated relaxin and Stat3 knockdown into CFs, which did not cause further downregulation of autophagy process and collagen protein compared with only Stat3 knockdown or relaxin treatment. These data suggested that relaxin ameliorates TGFß-induced fibrosis dependent on Stat3 signaling-mediated autophagy. This study uncovered a previously unrecognized antifibrotic role of relaxin in cardiac fibrosis, which is achieved through the inhibition of Stat3-dependent autophagy, implying a potential therapeutic target in fibrotic diseases.

A national survey of Chinese medicine doctors and clinical practice guidelines in China.

BACKGROUND: Clinical practice guidelines (CPGs) for Chinese medicine (CM) are being developed to assist doctors with appropriate decisions concerning CM care. To date, there has been little investigation on the perspectives of those to whom the guidelines are directed. METHODS: A self-administered questionnaire was sent to 4503 doctors in 28 provinces of China in the latter half of 2012. Questions were organized around the topics of knowledge, application, practice changes, beliefs and outcomes of implementation. Basic classificatory data on specialties and years of qualification were also collected. RESULTS: Replies were received from 4495 CM doctors (99.82%). Of these, 85.56% of CM doctors reported being familiar with CPG recommendations, but the overall adherence rate was only 50.39%. The length of time practicing CM may influence the rate of adherence, since 709 doctors (51.90%) with less than 5 years of experience reported never having followed CPGs. Doctors in nine specialties showed a modest degree of homogeneity in their attitudes towards CM diagnosis and treatment, which were generally positive. Most doctors regarded CPG-recommended therapies as safe (92%), economic (84%), and effective (76%). Approximately four-fifths of those questioned selected 'acceptable' (60.84%) and 'acceptable after revision' (19.23%) regarding their comprehensive assessment of the CPGs. CONCLUSIONS: An encouraging result from this survey is that the majority of CM doctors support the concept of CPGs for the practice of CM. However, the results of this survey also suggest that improving the adherence of CM doctors to the guidelines remains a major challenge to improving the practice standards for CM.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Internal Diseases in Traditional Chinese Medicine].

To evaluate the applicability and clinical applications of Guidelines for Diagnosis and Treatment of Internal Diseases in Traditional Chinese Medicine, so as to provide the basis for the revision of the guidelines. This study was completed by the research and promotion base for traditional Chinese medicine(TCM) standard. The methods of applicability evaluation and application evaluation were used in the study. The questionnaires were filled out to evaluate applicability of the guideline, including doctor's familiarity with the guideline,the quality of the guideline, applicable conditions and clinical applications. The prospective case study analysis method was used to evaluate application of the guideline, including evaluation of clinical application compliance and application results(such as clinical effects, safety and economy). There were two parts in the guideline, which were TCM guideline and Western medicine guideline. The results of applicability evaluation showed that there were no obvious differences between TCM guideline and Western medicine guideline in doctor's familiarity with guideline(85.43%, 84.57%) and the use of the guideline(52.10%, 54.47%); the guidelines with good quality, and higher scores in the scope of application and the use of the term rationality(91.94%, 93.35%); the rationality scores of relevant contents in syndrome differentiation and treatment were more than 75%; the applicable conditions were better, and the safety score was the the highest. The comprehensive applicability evaluation showed that the proportion of the application of TCM guideline and Western medicine guideline were 77.73%, 75.46%, respectively. The results of application evaluation showed that there was high degree coincidence between the guideline with its clinical application; except for "other treatment" and "recuperation and prevention" in TCM, other items got high scores which were more than 90%; in the evaluation of application effects, safety of the guideline was best, economy of the guideline was better, and clincal effect was good. The comprehensive application evaluation showed that 75%~80% doctors were satisfied with the guideline. The Guidelines for Diagnosis and Treatment of Internal Diseases in Traditional Chinese Medicine has been widely used in clinical practice, which is of high quality, high degree of clinical application,good safety and economy. But there were some disadvantages of the guideline such as lack of evidence-based medicine and innovation, which is need to be improved constantly in the guideline revision.

[Clinical application evaluation of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine].

Clinical application evaluation research of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine intends to evaluate the quality level and clinical application of the guideline. A questionnaire and prospective case survey methods were used to evaluate the applicability evaluation based on the clinician questionnaire and the application evaluation based on clinical case observation. The applicability evaluation, familiarity and utilization rate of doctors' guidelines were 85.06%, 62.76%; Sort by technical grade, intermediate grade doctors have a higher familiarity rate and utilization rate, while the junior grade doctor's is lower; Guide quality level of applicability evaluation, other items' rational percentage are better than 96% except the items of health preserving and prevention and other treatment is relatively low; Items' applicable percentage of applicability evaluation are more than 91% except the item of guide simplicity. Comprehensive applicability evaluation, The percentage of the guideline applicable to clinical practice accounted for 94.94%. The consistency rate of syndrome differentiation and clinical application is more than 96% in addition to prescription medication, other treatments and health preserving and prevention of the guidelines apply consistency of application evaluation. The percentage of good treatment effect accounted for 92.96% of application effect evaluation. The safety percentage is 99.89% and economy is 97.45%. The research shows that of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine quality level is good and is basically applicable to pediatric clinical practice which can be used as a standardized recommendation of pediatric common diseases' treatment specification. A small part of the guidelines are not applicable and need to be further consummated. Health preserving and prevention and other treatment of the guideline need to be revised.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine].

This study is to assess the Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine in clinical application and provide evidence for further guideline revision. The assessment was divided into applicability assessment and practicability assessment. The applicability assessment based on questionnaire survey and the traditional Chinese medicine (TCM) practitioners were asked to independently fill the Questionnaire for Applicability Assessment on the Guidelines for Diagnosis and Treatment in Traditional Chinese Medicine. The practicability assessment was based on prospective case investigation and analysis method and the TCM practitioners-in-charge filled the Case Investigation Questionnaire for Practicability Assessment on the Guidelines for Diagnosis and Treatment in Traditional Chinese Medicine. The data were analyzed in descriptive statistics. 151 questionnaires were investigated for applicability assessment and 1 016 patients were included for practicability assessment. The results showed that 88.74% of them were familiar with the guidelines and 45.70% used them. The guidelines quality and related items were similar in applicability assessment and practicability assessment, and scored highly as more than 85.00% except the "recuperating and prevention". The results suggested that the quality of Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine was high and could better guide the clinical practice. The "recuperating and prevention" part should be improved and the evidence data should be included in future guideline revision, so that the clinical utilization rate could be increased.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Common Diseases of Coloproctology in Traditional Chinese Medicine].

To provide reference for revising the Guidelines for Diagnosis and Treatment of Common Diseases of Coloproctology in Traditional Chinese Medicine (TCM) through clinical research. 9 TCM hospitals worldwide have conducted a survey and questionnaires for 7 CPGs have been received. 263 cases clinical doctors accepted the applicability survey of guidelines. 89.35% is more familiar to the guidelines and 36.12% have been used the guidelines. In syndrome differentiation and treatment related contents, diagnostic point, treatment and syndrome differentiation are higher, accounted for 96.96%, 88.59%, 96.20%, respectively. Rationality of prevention is lower, accounted for 65.02%.88.21% clinical doctors believe that the Guidelines for Diagnosis and Treatment of Common Diseases of Coloproctology in Traditional Chinese Medicine is applicable. The application of the guidelines is evaluated by prospective observation of 1 309 cases. The higher consistency between guidelines and clinical practice is Western medicine disease diagnosis and traditional Chinese medicine disease diagnosis, accounted for 98.70%, 90.76%, respectively. The lower is rationality of prevention, accounted for 49.27%. The safety and economy of the guidelines are better, accounted for 97.02%, 95.11%, respectively. The comprehensive evaluation results showed that the overall treatment effect and technical level, satisfaction degree, applicability in clinical practice which were 7-9 points is 81.52%, 80.60%, 79.30%.The complex evaluation of diagnosis and treatment of common diseases of coloproctology in TCM guidelines is good, and suitable for clinical application with increase the content of rationality of prevention.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine].

To evaluate the clinical applicability and application of Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine, 11 diseases from Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine were evaluated by methods of questionnaire and prospective case study at 16 construction units for traditional Chinese medicine standards research and extension. Results showed that 361 clinical doctors accepted the applicability survey of guidelines, and 87.26% of them were more familiar to the guideline and 25.21% of them used the guideline. In syndrome differentiation and treatment related contents, rationality of prescription medication and syndrome classification was higher, accounted for 91.69% and 86.98% respectively, but the rationality of recuperation prevention was lower, accounted for 44.6%. 75.62% clinical doctors believed that the Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine was applicable. The application of the guidelines is evaluated by prospective observation of 2 935 cases. The higher compliance between the guideline and clinical practice was present in TCM (traditional Chinese medicine) disease diagnosis and WM (western medicine) disease diagnosis, accounted for 98.30% and 94.11% respectively. The lower compliance was present in recuperation prevention, accounted for 59.39%. The safety and economy of the guideline was higher, accounting for 95.64%, 94.75%, respectively. The comprehensive evaluation results showed that the rate of the overall treatment effect with technical level, satisfaction degree or applicability in clinical practice which were 7-9 points is 77.38%, 74.00%, 76.90% respectively. This guideline has a high clinical compliance and can be used as a standard for common diseases of gynecology, but there are also some conditions with poor applicability, which does not conform to the actual situation, and needs to be further revised.