Assessing the temporal within-day glycemic variability during hospitalization in patients with type 2 diabetes patients using continuous glucose monitoring: a retrospective observational study.

AIMS: Frequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV. METHODS: We conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models. RESULTS: A total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77-0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69-0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01-1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02-1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55-0.75; IRR: 0.86, 95% CI: 0.79-0.93) and glinide (HR: 0.47, 95% CI: 0.31-0.73; IRR: 0.84, 95% CI: 0.73-0.97) may lead to an increased frequency of within-day GV. CONCLUSIONS: An increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV.

Promising Natural Medicines for the Treatment of High-Altitude Illness.

Li Li, Lin Lin, Bo Wen, Peng-cheng Zhao, Da-sheng Liu, Guo-ming Pang, Zi-rong Wang, Yong Tan, and Cheng Lu. Promising natural medicines for the treatment of high-altitude illness. High Alt Med Biol. 24:175-185, 2023.-High-altitude illness (HAI) is a dangerous disease characterized by oxidative stress, inflammatory damage and hemodynamic changes in the body that can lead to severe damage to the lungs, heart, and brain. Natural medicines are widely known for their multiple active ingredients and pharmacological effects, which may be important in the treatment of HAI. In this review, we outline the specific types of HAI and the underlying pathological mechanisms and summarize the currently documented natural medicines applied in the treatment of acute mountain sickness and high-altitude cerebral edema, high-altitude pulmonary edema, chronic mountain sickness, and high-altitude pulmonary hypertension. Their sources, types, and medicinal sites are summarized, and their active ingredients, pharmacological effects, related mechanisms, and potential toxicity are discussed. In conclusion, natural medicines, as an acceptable complementary and alternative strategy with fewer side effects and more long-term application, can provide a reference for developing more natural antialtitude sickness medicines in the future and have good application prospects in HAI treatment.

The construction of a TCM knowledge graph and application of potential knowledge discovery in diabetic kidney disease by integrating diagnosis and treatment guidelines and real-world clinical data.

Background: The complexity and rapid progression of lesions in diabetic kidney disease pose significant challenges for clinical diagnosis and treatment. The advantages of Traditional Chinese Medicine (TCM) in diagnosing and treating this condition have gradually become evident. However, due to the disease's complexity and the individualized approach to diagnosis and treatment in Traditional Chinese Medicine, Traditional Chinese Medicine guidelines have limitations in guiding the treatment of diabetic kidney disease. Most medical knowledge is currently stored in the process of recording medical records, which hinders the understanding of diseases and the acquisition of diagnostic and treatment knowledge among young doctors. Consequently, there is a lack of sufficient clinical knowledge to support the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine. Objective: To build a comprehensive knowledge graph for the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine, utilizing clinical guidelines, consensus, and real-world clinical data. On this basis, the knowledge of Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was systematically combed and mined. Methods: Normative guideline data and actual medical records were used to construct a knowledge graph of Traditional Chinese Medicine diagnosis and treatment for diabetic kidney disease and the results obtained by data mining techniques enrich the relational attributes. Neo4j graph database was used for knowledge storage, visual knowledge display, and semantic query. Utilizing multi-dimensional relations with hierarchical weights as the core, a reverse retrieval verification process is conducted to address the critical problems of diagnosis and treatment put forward by experts. Results: 903 nodes and 1670 relationships were constructed under nine concepts and 20 relationships. Preliminarily a knowledge graph for Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was constructed. Based on the multi-dimensional relationships, the diagnosis and treatment questions proposed by experts were validated through multi-hop queries of the graphs. The results were confirmed by experts and showed good outcomes. Conclusion: This study systematically combed the Traditional Chinese Medicine diagnosis and treatment knowledge of diabetic kidney disease by constructing the knowledge graph. Furthermore, it effectively solved the problem of "knowledge island". Through visual display and semantic retrieval, the discovery and sharing of diagnosis and treatment knowledge of diabetic kidney disease were realized.

To Investigate the Potential Mechanism of Huanglian Jiangtang Formula Lowering Blood Sugar in View of Network Pharmacology and Molecular Docking Technology.

Objective: In view of network pharmacology and molecular docking technology, to explore the targets as well as effect mechanism of the Huanglian Jiangtang formula (including Coptis chinensis, Anemarrhena asphodeloides, rhubarb wine, Cortex Moutan, Rehmannia glutinosa, and dried ginger) in the type II diabetes therapy. Methods: TCMSP and Batman database (DB) were used to retrieve the chemical components and action targets of drugs; GeneCards, OMIM, TTD, DrugBank, and other databases were applied to screen the disease targets. We used the UniProt DB to annotate the targets before building the drug-compound-target network with Cytoscape 3.9.1. We also exploited the String DB to construct the protein-protein interaction (PPI) network. In addition, the targets for the treatment of type II diabetes were searched in the DrugBank, OMIM, GeneCards, and TTD database; then, we utilized Venn to intersect the key targets for the therapy of type II diabetes and active ingredient targets to obtain common targets. Furthermore, we exploited the common targets using GO and KEGG enrichment analysis method. The common targets and core components were analyzed by molecular docking using the AutoDock software. Results: A total of 61 effective components of this compound were screened out; drugs and type II diabetes have 278 common targets; the PPI network screened core target proteins such as CDKN1A, CDK2, and E2F1 with the help of molecular docking technology; the three main compounds including quercetin, kaempferol, and gamma-aminobutyric acid were obtained. Besides, the key target proteins had excellent binding properties with the main components. The signal pathways of six compound interventions in type II diabetes were mostly related to cancer, cocaine addiction, aminoacyl-tRNA biosynthesis, glycine, serine, threonine metabolism, platinum drug resistance, and other pathways, according to the KEGG enrichment analysis method. Conclusion: In the treatment of diabetes, the Huanglian Jiangtang formula has sorts of properties especially in the aspects of composition, target, and pathway. Its molecular target and mechanism of action may be related to pathways in cancer, cocaine addiction, aminoacyl-tRNA biosynthesis, glycine, serine, threonine metabolism, platinum drug resistance, and other pathways. This conclusion can provide theoretical support and science for further research.

Human serum metabolomic analysis reveals progression for high blood pressure in type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the most ordinary metabolic disorders and manifests as a high blood sugar level; 80%-90% of patients with T2DM will develop high blood pressure (HBP), which exacerbates irreversible organ damage. Understanding the metabolic basis of HBP is essential to facilitating early diagnosis and prompt treatments of diabetic complications. RESEARCH DESIGN AND METHODS: 34 patients who originally had T2DM and then developed HBP within 1 year were selected from physical examination participants. Using ultrahigh-performance liquid chromatography quadrupole time-of-flight metabolomic analysis, we compared the metabolomic profile of patients with 30 healthy controls. The results showed a clear discrimination in metabolomic profiles between T2DM and T2DM+HBP when employing orthogonal projection to latent structure with discriminant analysis with electrospray ionization modes. RESULTS: Eight differential metabolites changed significantly during disease progression, among which L-isoleucine, L-glutamic acid, pyroglutamic acid and linoleic acid decreased, while sphinganine, Cer(d18:0/16:0), Cer(d18:0/18:0), and citric acid increased. These metabolites are associated with the γ-glutamyl cycle, tricarboxylic acid cycle, and ceramide metabolism. CONCLUSIONS: These novel serum biomarkers may improve the management of T2DM and HBP complications, thus reducing the use of incorrect medical care.

Probiotics protect against RSV infection by modulating the microbiota-alveolar-macrophage axis.

Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-ß. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-ß in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future.

Synergistic effects of anti-MRSA herbal extracts combined with antibiotics.

MRSA is a super drug-resistant bacterium. Developing new drug or therapeutic strategies against MRSA is urgently needed. Increasing evidence has shown that herbal extracts and antibiotics can have synergistic effects against MRSA. This review focuses on commonly used antibiotics combined with herbal extracts against MRSA and the corresponding mechanisms. Through systematic analysis, we found that herbal extracts combined with antibiotics, such as ß-lactams, quinolones, aminoglycosides, tetracyclines and glycopeptides, could greatly enhance the antibacterial effects of the antibiotics, reduce the dosage and toxic side effects, and reverse MRSA resistance. Therefore, we conclude that herbal extracts combined with antibiotics may be a promising strategy to combat MRSA. This review provides a novel idea for overcoming antibiotic resistance.

Is dietary fat associated with the risk of age-related macular degeneration? Protocol for a systematic review and meta-analysis.

Previous studies evaluating the association of dietary fat and risk of age-related macular degeneration (AMD) yield discrepant results. The objective of this systematic review (SR) and meta-analysis is to establish whether an association exists between dietary fat and AMD. This protocol was developed in line with the quality requirements of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. PubMed and EMBASE will be searched for randomized controlled trials (RCTs), non-randomized trials (NRTs), cross-sectional studies, cohort studies, and case-control studies that evaluate the total incidence of AMD. The data extraction content and quantitative analysis will be carried out systematically. Newcastle-Ottawa Scale (NOS), the Cochrane risk of bias tool, and quality assessment tools will be used for quality assessment. This SR will synthesize evidence to determine if there is an association between dietary fat and AMD. The evidence would provide rationale for future research and serve as a basis for the development of future guidelines. Results are expected to be publicly available in mid 2020.PROSPERO registration number: CRD42019137086.

Zhuang Gu Guan Jie Wan: Reasonable Application Can Alleviate the Liver Injury for Osteoarthritis Treatment.

The potential toxicity of herbal drugs, particularly drug-induced liver injury (DILI), has received extensive attention as the use of Chinese herbal medicine has rapidly increased globally. As a classic Chinese patent medicine, Zhuang Gu Guan Jie Wan (ZGGJW) has been brought into focus recently because of its satisfactory therapeutic effects on osteoarthritis (OA) as well as its unanticipated side effects. This study aimed to decipher the puzzling phenomenon of liver injury developing in response to ZGGJW that varies by the subtype of OA. Normal, anterior cruciate ligament transaction (ACLT) and partial medial meniscectomy (MMx) induced OA and ovariectomy combined with ACLT and partial MMx induced rat models were used and treated orally with ZGGJW or distilled water for 30 days. The results from histopathology, biochemistry, and immunohistochemistry showed that ZGGJW induced liver injury, increased the level of malondialdehyde (MDA), and decreased the levels of total antioxidation capability (T-AOC), superoxide dismutase (SOD), interleukin-22 (IL-22), and signal transducer and activator of transcription factor 3 (STAT3) in the liver of normal rats, while liver injury was alleviated and showed different tendencies in the above markers for ACLT and partial MMx induction rats and ovariectomy combined with ACLT and partial MMx induction rats after ZGGJW treatment. In the OA disease states, hepatic injury induced by ZGGJW could be associated with an impairment in antioxidant capacity and the high levels of IL-22 and STAT3 after ZGGJW treatment may be responsible for the slight hepatic injury of ZGGJW based on the subtype of OA. This study provides a novel approach to better understanding of the risks and limitations when using potentially toxic Chinese patent medicine in clinical applications.

Hei-Gu-Teng Zhuifenghuoluo Granule Modulates IL-12 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a type of chronic systemic inflammatory disease; it has a very complicated pathogenesis, and multiple pathological changes are implicated. Traditional Chinese medicine (TCM) like Tripterygium wilfordii Hook. F. or Sinomenium acutum (Thunb.) Rehd et Wils. has been extensively used for centuries in the treatment of arthritic diseases and been reported effective for relieving the severity of RA. Hei-Gu-Teng Zhuifenghuoluo granule (HGT) which contains Periploca forrestii Schltr., Sinomenium acutum (Thunb.) Rehd et Wils., and Lysimachia paridiformis Franch. var. stenophylla Franch. was a representative natural rattan herb formula for the treatment of RA in China, but the mechanism has not been elucidated. This study aimed at exploring the mechanism of HGT on RA using the bioinformatics analysis with in vivo and in vitro experiment validation. The potential action mechanism was first investigated by bioinformatics analysis via Ingenuity Pathway Analysis (IPA) software. After that, we use experimental validation such as collagen-induced arthritis (CIA) mice model in vivo and U937 cell model in vitro. The bioinformatics results suggested that HGT may have anti-inflammatory characteristic on RA and IL-12 signaling pathway could be the potential key trigger. In vivo experiments demonstrated that HGT ameliorated the symptoms in CIA mice and decreased the production of inflammatory cytokines in both mice ankle joints and serum. Furthermore, HGT effectively inhibited the activation of IL-12R and STAT4 on IL-12 signaling pathway. In vitro experiments showed that HGT inhibited the production of IL-12R and STAT4 induced by IL-12 in lipopolysaccharide- (LPS-) stimulated U937 cells. Moreover, IL-12R knockdown was able to interfere with the inhibition effects of HGT on the production of these cytokines. Our results confirmed the anti-inflammatory property of HGT, which was attributed to its inhibition on IL-12 signaling pathway.

Association between Body Mass Index and Health-Related Quality of Life: The "Obesity Paradox" in 21,218 Adults of the Chinese General Population.

BACKGROUND: There was no consistent recognition of the association between high or low body mass index (BMI) and health related quality of life (HRQL). The aim of this research was to study the association between BMI and HRQL in Chinese adults, and to further explore the stability of that association in the subgroup analysis stratified by status of chronic conditions. METHODS: A total of 21,218 adults aged 18 and older were classified as underweight, normal weight, overweight, class I obese, and class II obese based on their BMI. HRQL was measured by the SF-36 Health Survey. The independent impact of each BMI category on HRQL was examined through standard least squares regression by comparing the difference of SF-36 scores and the minimum clinically important differences (MCID), which was defined as 3 points. RESULTS: Compared to the normal weight, the class I obese was significantly associated with better HRQL scores in the mental component summary (MCS) (75.1 vs. 73.4, P<0.001). The underweight had the lowest score in both the physical components summary (PCS) (75.4 vs. 77.5, P<0.001) and mental components summary (MCS) (71.8 vs. 73.4, P<0.001). For the MCID, the HRQL score was reduced by more than 3 points in the physical functioning for the class II obese (D=-3.43) and the general health for the underweight (D=-3.71). Stratified analyses showed a similar result in the health subjects and chronic conditions, and it was significant in the chronic conditions. CONCLUSIONS: The class I obese showed the best HRQL, especially in the mental domain. The worst HRQL was found in the underweight. The class II obese reduced HRQL in the physical functioning only. "Obesity paradox" was more obvious in the participants with chronic conditions.

[Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity].

OBJECTIVE: To explore the relationships between traditional Chinese medicine (TCM) constitutional types and overweight or obesity so as to provide evidence for adjusting constitutional bias and preventing and treating obesity. METHODS: The data comes from a cross-sectional survey on TCM constitution of 18 805 samples aged above 18 in Beijing and 8 provinces (Jiangsu, Anhui, Gansu, Qinghai, Fujian, Jilin, Jiangxi and Henan) in China. The survey of TCM constitution was performed by standardized constitution in Chinese medicine questionnaire (CCMQ). Discriminatory analysis method was used to judge the individual's constitutional type (gentleness type, qi-deficiency type, yang-deficiency type, yin-deficiency type, phlegm-dampness type, dampness-heat type, blood-stasis type, qi-depression type and special diathesis type). The relationships between TCM constitution types and overweight or obesity was investigated by logistic regression analysis. RESULTS: Compared with gentleness type, the risk of overweight (OR, 2.05; 95% CI, 1.79-2.35) and obesity (OR, 4.34; 95% CI, 3.52-5.36) in phlegm-dampness type is significantly increased; the risk of obesity (OR, 1.60; 95% CI, 1.30-1.98) in qi-deficiency type is significantly higher; the risk of overweight and obesity in yang-deficiency type, blood-stasis type, and qi-depression type is significantly lower. CONCLUSION: Phlegm-dampness type and qi-deficiency type are the main constitutional risk factors of overweight or obesity.

[Changes of endocrine and immune function in subjects of yang deficiency constitution].

OBJECTIVE: To investigate the changes of endocrine, cyclic nucleotide and immune systems in subjects of yang deficiency constitution, and to explore the relationship among characteristics and causes of yang deficiency constitution, the physiological and biochemical parameters. METHODS: Based on the diagnostic criteria for the clinical epidemiological investigation, sixty subjects of yang deficiency constitution and fifty of normal constitution were selected. Eight milliliters venous blood were taken from overnight fasted subjects at 8:00-9:00. The sera were obtained by centrifugation of the blood at the speed of 3000 r/min for 5 minutes, and they were stored at -70 degrees C until use. The serum levels of corticosterone, cortisol, adrenocorticotrophic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropic-stimulating hormone (TSH), interleukin-1beta and interleukin-2 were measured by enzyme-linked immunosorbent assay; the cAMP/cGMP ratio was also computed; and the differences of the above indexes were compared between the two types of subjects. RESULTS: The serum levels of corticosterone, interleukin-1beta, TSH and cAMP/cGMP ratio of yang deficiency constitution significantly increased as compared with those of normal constitution, and the serum levels of cortisol, ACTH, cGMP and FT4 of yang deficiency constitution significantly decreased in comparison with those of normal constitution. CONCLUSION: Subjects of yang deficiency constitution may be not only related to hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-thyroid axis, but also related to the functional disorders of cyclic nucleotide and immune systems.