Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling.

Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability, leading to severe cardiovascular events. In this study, we demonstrate that elevated serum levels of palmitic acid, a type of saturated fatty acid, are significantly linked to this enhanced vulnerability in patients with Type 2 Diabetes Mellitus. Through a combination of human cohort studies and animal models, our research identifies a key mechanistic pathway: palmitic acid induces macrophage Delta-like ligand 4 signaling, which in turn triggers senescence in vascular smooth muscle cells. This process is critical for plaque instability due to reduced collagen synthesis and deposition. Importantly, our findings reveal that macrophage-specific knockout of Delta-like ligand 4 in atherosclerotic mice leads to reduced plaque burden and improved stability, highlighting the potential of targeting this pathway. These insights offer a promising direction for developing therapeutic strategies to mitigate cardiovascular risks in patients with Type 2 Diabetes Mellitus.

Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities.

Macrophages are key players in the immune response and have been implicated in various human diseases, including atherosclerosis, cancer, and chronic inflammatory disorders. While numerous studies have delved into the nuances of macrophage behavior in these conditions, there remains a gap in understanding the specific role of Delta-like ligand 4 (Dll4)-expressing macrophages and their overarching implications across these diseases. Among the plethora of factors expressed by macrophages, Dll4 has emerged as a molecule of particular interest. Recent studies have highlighted its unique role in modulating macrophage functions and its potential implications in various diseases. This review seeks to consolidate existing knowledge, address this gap, and present a comprehensive overview of Dll4-expressing macrophages in the context of these disorders and highlight their potential as therapeutic targets. We examined the involvement of Dll4-expressing macrophages in multiple human diseases such as atherosclerosis, cancer and chronic inflammatory diseases, emphasizing their influence on disease progression. We also discussed the challenges, limitations, and emerging research areas in targeting Dll4-expressing macrophages and provide an outlook on potential therapeutic strategies for the treatment of these diseases. By addressing the previously existing research gap, we've provided a roadmap that brings together fragmented insights, paving the way for more holistic research and potentially more effective therapeutic strategies centered on Dll4-expressing macrophages.

Appraisal of the Quality and Contents of Clinical Practice Guidelines for Hypertension Management in Chinese Medicine: A Systematic Review.

OBJECTIVE: To evaluate the quality and consistency of recommendations in the clinical practice guidelines (CPGs) for hypertension in Chinese medicine (CM). METHODS: CM CPGs were identified from 5 electronic databases and hand searches through related handbooks published from January 1990 to December 2013. Three reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and compared the CPGs' recommendations on CM syndrome pattern classification and treatment. RESULTS: Five CM CPGs for hypertension were included. The quality score of the evidence-based (EB) guideline was higher than those of the consensus-based with no explicit consideration of evidence-based (CB-EB) and the consensus-based (CB) guidelines. Three out of five patterns in the CPGs were recommended by the EB guideline. Tianma Gouteng Formula () in the EB guideline was recommended mostly for hypertension patients with pattern of ascendant hyperactivity of Gan (Liver)-yang and pattern of yin deficiency with yang hyperactivity in the CPGs. Acupuncture and massage were recommended for Grade I and Grade II hypertension with severe symptoms weakening the quality of life in the EB guideline. For Grade I and Grade II hypertension, CM could be used alone, while for Grade III hypertension, they should be used in combination with Western medicines. CONCLUSION: The quality of EB guideline was higher than those of CB and CB-EB CPGs in CM for hypertension and CM should be prescribed alone or combined with Western medicines based on the grade of hypertension.

[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 Cancer in Traditional Chinese Medicine].

This study aims to evaluate the adaptability and applicability of Guidelines for the Diagnosis and Treatment of Cancer in Traditional Chinese Medicine. The assessment methods included adaptability assessment and applicability assessment. The adaptability assessment was based on the questionnaire survey to evaluate the familiarity, utilization, quality, and clinical application of the Guidelines; applicability assessment was based on the prospective observation of 853 clinical cases to investigate the applicability and effect of the Guidelines, including effectiveness, economy and safety. Statistical analysis for basic description, construction of different comparison groups for cross or hierarchical statistical test, multi-factor analysis, and confounding factors were used in the study. Adaptability assessment results showed that 63.03% of TCM doctors considered guidelines as good or very good applicability and 4.24% of TCM doctors considered guidelines with very poor applicability in clinical practice. For the applicability evaluation, TCM doctors considered that the "overall efficacy and technology level", "satisfactory degree" and "adaptability in clinical practice" of the guideline were 85.46%, 80.43% and 69.40% respectively. The results showed that guideline was well known among TCM doctors, especially junior TCM doctors. Adaptability and applicability of Guidelines were totally good but the quality and adaptability of the intervention schemes were still week, so the quality of Guidelines should be improved by revision.

[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.

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.

[Methodological quality assessment of community-acquired pneumonia clinical practice guidelines in China based on AGREE â ¡ tool].

This study is aimed to identify and assess the methodological quality of community-acquired pneumonia (CAP) clinical practice guidelines (CPG) in China by using AGREE Ⅱ tool. CNKI, SinoMed, Wanfang, and VIP Chinese databases from database establishment to March 2017 were searched by manual retrieval to collect all the clinical practice guidelines prepared by various associations or organizations, then AGREE Ⅱtool was used to assess them. Data in each CPG were analyzed in terms of six domains, including scope and purpose, participants, rigor, clarity and readability, applicability and editorial independence. A total of 4 CPGs were included. The results showed that the scope and purpose scored 45.8%; the clarity of expression scored 44.75%; the participants scored 31.9%; the rigor scored 18.98%; the applicability scored 7%; and finally the editorial independence scored 1%. It is concluded that the quality of applicability and the editorial independence should attained paid more attention in future development or updating of the guidelines. In addition to strengthening the compliance with international general principles, we should also pay attention to the characteristics of traditional Chinese medicine treatment, especially the related evidences as complementary and alternative treatment for western intervention measures.

The add-on effect of a Chinese herbal formula for patients with resistant hypertension: study protocol for a pilot cohort study.

BACKGROUND: Despite a recent American Heart Association (AHA) consensus statement emphasizing the importance of resistant hypertension (RH), its control is still a challenge for conventional medicine. The Chinese herbal formula, Qutan Huayu Fang, has been used effectively to assist antihypertensive agents in blood pressure control, but its effect for RH patients is still unclear. This pilot study aims to explore the effects of taking the formula in addition to antihypertensive medication in the management of RH. METHODS/DESIGN: A prospective cohort study will be conducted in two first-class hospitals of traditional Chinese medicine (TCM). Eligible RH patients will be classified as the experimental group (n = 100) and the control group (n = 100) based on the interventions they receive. Participants taking antihypertensive agents and the Chinese herbal formula will be in the experimental group and those taking antihypertensive agents alone will be in the control group. The whole study will last 24 weeks, including an 8-week observation and follow-up at 24 weeks. The primary outcomes, assessed against patient baseline conditions, will be the reduction of systolic blood pressure and diastolic blood pressure as well as changes in TCM symptoms and signs. These outcomes will be assessed at weeks 2, 4, 6, and 8. The reductions of blood pressure will also be assessed at week 24. Cardiac events and mortality rate will be secondary outcomes and will be assessed at weeks 8 and 24. Any adverse reactions will be recorded during the study. The causal inference method will be used to assess the effectiveness of the inclusion of TCM herbal medicine in the management of patients with RH. DISCUSSION: This study will determine whether the Chinese herbal formula is helpful for RH patients treated with antihypertensive agents and the findings will provide a basis for further confirmatory studies.

Appraisal of clinical practice guidelines for ischemic stroke management in Chinese medicine with appraisal of guidelines for research and evaluation instrument: A systematic review.

OBJECTIVE: To systematically review the clinical practice guidelines (CPGs) for ischemic stroke in Chinese medicine (CM) with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. METHODS: CM CPGs for ischemic stroke were searched in 5 online databases and hand-searches in CPGrelated handbooks published from January 1990 to December 2012. The CPGs were categorized into evidence based (EB) guideline, consensus based with no explicit consideration of evidence based (CB-EB) guideline and consensus based (CB) guideline according to the development method. Three reviewers independently appraised the CPGs based on AGREE II instrument, and compared the CPGs' recommendations on CM pattern classification and treatment. RESULTS: Five CM CPGs for ischemic stroke were identified and included. Among them, one CPG was EB guideline, two were CB guidelines and two were CB-EB guidelines. The quality score of the EB guideline was higher than those of the CB-EB and CB guidelines. Five CM patterns in the CPGs were recommended in the EB CPG. The comprehensive protocol of integrative Chinese and Western medicine recommended in the EB CPG was mostly recommended for ischemic stroke in the CPGs. The recommendations varied based on the CM patterns. CONCLUSION: The quality of EB CPG was higher than those of CB and CB-EB CPGs in CM for ischemic stroke and integrative approaches were included in CPGs as major interventions.

[Study on path of transforming traditional Chinese medicine research achievement into guideline].

At present, a number of scientific research achievements has been formed. Scientific achievement is the crystallization of great efforts from scientific workers, and it's also the valuable treasure of human civilization. Standardization is an important way to promote the international communication of Chinese medicine, and it's significant in boosting China's scientific and technological progress, improving market competitiveness and promoting international trade. Transformation of scientific research to the guideline is not only beneficial to improving the technology content of the standard, but also to the conversion from scientific research achievements into productivity. Therefore, only by absorbing the advanced scientific and technological achievements, reproducing the theory of traditional Chinese medicine (TCM) and medical technology in standard form, can make TCM keep pace with the times. This study preliminarily explores for the method to transform scientific research achievements into guideline, in order to provide reference for the future technical specifications, thus to further the development of TCM.

Expert consensus on the treatment of hypertension with chinese patent medicines.

Objectives. This study was aimed to determine the therapeutic principle and identify Chinese Patent Medicine (CPM) with corresponding indications for hypertension treatment. Methods. Three rounds of Delphi survey were mailed among 40 cardiovascular integrative medicine specialists. Items with agreement of more than 80% respondents were included in the consensus. Results. According to majority of the panelists, CPM is suitable for most hypertensive patients and should be used according to traditional Chinese medicine pattern classification. CPM could be used alone for grade 1 hypertension and could be used in combination with Western biomedicine (WM) for both grade 2 and grade 3 hypertension. It is recommended that less than two CPMs are used simultaneously. For the treatment of grade 2 and 3 hypertension, CPM and WM should be taken separately. Recommended CPMs included Tianma Gouteng granule, Qiju Dihuang capsule, Jinkui Shenqi pill, Yinxingye tablet, Niuhuang Jiangya pill and Banxia Tianma pill. The indications of 4 CPMs were specified with symptoms related to TCM pattern classification by the experts. Conclusions. An expert consensus on CMP application was formed for the treatment of hypertension in the form of integrative medicine. A flow of IM hypertension management was proposed based on the results of the survey.

Evaluation of the conjoint efficacy in Chinese medicine with the longitudinal latent variable linear mixed model.

Chinese medicine (CM) clinical efficacy evaluation research involves the longitudinal multivariate measurement which means that patients are measured repeatedly and each patient is measured by several indicators on each fixed cross-section. Although each indicator can be evaluated separately with a longitudinal linear mixed model, it is important to consider all the endpoints together especially when researchers pay special attention to the change of the conjoint efficacy for several indicators in one patient. In this article, we introduce a latent variable linear mixed model to the CM conjoint efficacy evaluation and discuss why and how to analyze the longitudinal multivariate endpoint data in the clinical CM efficacy evaluation research. It may lead to the new insight of using such methodology in the field of conjoint efficacy evaluating of CM study. And with the definition of syndrome and symptom in the CM theory, the applied discussion brings the insight of CM syndrome evaluating in future. We illustrate this methodology using an example of CM efficacy evaluation from an ischemic stroke research.

Development of clinical practice guidelines in 11 common diseases with Chinese medicine interventions in China.

OBJECTIVE: To analyze the clinical practice guideline (CPG) development on 11 common diseases with Chinese medicine (CM) interventions in China. METHODS: The CPGs of 11 common diseases which could be treated effectively with CM had been published between 1980 and 2010 in China. The 11 diseases include coronary heart disease (angina pectoris), hypertension, chronic gastritis, rheumatoid arthritis, cerebral infarction, migraine, diabetes, primary osteoporosis, insomnia, common cold, and IgA nephropathy. The issuing organization, date of publication, development methods, and citation rate of the CPGs were analyzed. According to the development method, each guideline was categorized as consensus-based (CB), evidence-based (EB), or consensus based with no explicit consideration of evidence-based (CB-EB). RESULTS: Thirty-three CPGs on the 11 common diseases were found: 20 guidelines were classified as CB, 13 as CB-EB and none as EB. Fifteen CPGs were issued by the China Association of Chinese Medicine, 8 by professional working groups, and 4 by the State Administration of Traditional Chinese Medicine. Six guidelines were published between 1980 and 1990, 9 between 1991 and 2000, and 18 between 2001 and 2010. Fifty-eight percent of these guidelines have not been amended timely. Only 54.5% (18/33) of the 33 guidelines were cited by other researchers and 45.5% (15/33) percent had never been cited. CONCLUSIONS: Most CPGs developed for 11 common diseases with CM approaches in China are consensus, and their citation rates are relatively low. The results suggest that more EB CPG or CPG strictly based on expert consensus could be developed, and great efforts should be made for future CM CPG application.

Study on canceration law of gastric mucosal dysplasia based on syndromes of Chinese medicine.

OBJECTIVE: To study the syndrome evolution law of Chinese medicine (CM) in the patients with gastric mucosal dysplasia. METHODS: Three hundred and twenty four gastric mucosal dysplasia patients with deficiency and excess correlation syndromes were enrolled by a multi-center collaboration for two years' clinical follow-up to detect the levels of tumor supplied group of factors (TSGF) and carcino-embryonic antigen (CEA). RESULTS: Among the 324 cases, 29 cases turned cancer in the two years, and the canceration rate was 9.0%. The three syndromes with higher canceration rate were the damp-heat accumulating Wei syndrome concurring or combining with asthenia-cold in Pi and Wei syndrome for 16.7%; stagnation in Wei collaterals syndrome concurring or combining with asthenia of both qi and yin syndrome for 13.2%; stagnation of Gan and Wei qi syndrome concurring or combining with asthenia-cold in Pi and Wei syndrome for 8.0%, respectively. Among the three syndromes, the highest level of TSGF occurred in the former two syndromes. In the half year before carcinogenesis, the syndromes of the patients took on deficiency and excess concurrent syndromes, and the deficiency syndromes involving the qi and blood deficiency syndrome and the Shen deficiency syndrome accounting for 48.0%. CONCLUSIONS: Gastric mucosal dyspalsia canceration syndromes took on the polymorphism of excess and deficiency concurrent syndromes and had the characteristics of deficiency syndromes involving qi and blood deficiency syndrome and Shen-yin-yang deficiency syndrome.

[Thinking on methods for formulating development strategy of traditional Chinese medicine standardization].

Traditional Chinese medicine (TCM) standardization serves as an important foundation of TCM modernization and internationalization, and TCM standardization strategy is the core of the subject. Recently, some developed countries and developing countries with a better economic basis have set development strategy for TCM standardization. China is at the beginning on TCM standardization strategy study. This paper explored the methods for setting TCM standardization development strategy. Firstly, strengths, weaknesses, opportunities and threats of TCM were analyzed based on SWOT method to set development tactics. On the above basis, the authors defined the total goal and stage goal under the guidance of the relevant laws and regulations. To achieve the strategic goal, priority areas were formed by literature analysis and expert inquiry method, and the safeguard measures were formulated by expert symposium. Secondly, the draft for development strategy of TCM standardization was made based on the above content. Finally, the authors revised and formed the official development strategy of TCM standardization.

Effect of Jinguo Weikang Capsule on proto-oncogene expression of gastric mucosa in rats with gastric precancerous lesions.

OBJECTIVE: To study the effect of Jinguo Weikang Capsule [see text] on the gene expression of H-ras, epidermal growth factor receptor (EGFR), P53 and C-myc of the gastric mucosa in rats with gastric precancerous lesions, and to investigate the action mechanism of JWC on gastric precancerous lesions. METHODS: A rat model with paratypical proliferation of the gastric epithelium mucosa was established by using 60Co irradiation. Rats were divided into the normal group, model group, high-, medium-, low-dose JWC treatment groups, and the vitacoenzyme control group, and were treated for 30 days. The expression of H-ras, EGFR, P53 and C-myc genes of the gastric mucosa was detected by using immunohistochemical methods. RESULTS: The expression and over-expression rates of H-ras, EGFR, P53 and C-myc gene in the high-and medium-dose JWC treatment groups were significantly lower (P<0.05) as compared with those of the model group. CONCLUSION: JWC can inhibit the expression of the H-ras, EGFR, P53 and C-myc genes expression of the gastric mucosa in rats, which may be one of mechanisms involved in suppressing or reversing gastric carcinogenesis.