Establishment and Verification of an Artificial Intelligence Prediction Model for Children With Sepsis.

BACKGROUND: Early identification of high-risk groups of children with sepsis is beneficial to reduce sepsis mortality. This article used artificial intelligence (AI) technology to predict the risk of death effectively and quickly in children with sepsis in the pediatric intensive care unit (PICU). STUDY DESIGN: This retrospective observational study was conducted in the PICUs of the First Affiliated Hospital of Sun Yat-sen University from December 2016 to June 2019 and Shenzhen Children's Hospital from January 2019 to July 2020. The children were divided into a death group and a survival group. Different machine language (ML) models were used to predict the risk of death in children with sepsis. RESULTS: A total of 671 children with sepsis were enrolled. The accuracy (ACC) of the artificial neural network model was better than that of support vector machine, logical regression analysis, Bayesian, K nearest neighbor method and decision tree models, with a training set ACC of 0.99 and a test set ACC of 0.96. CONCLUSIONS: The AI model can be used to predict the risk of death due to sepsis in children in the PICU, and the artificial neural network model is better than other AI models in predicting mortality risk.

miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Propyl gallate exposure affects the mouse 2-cell stage embryonic development through inducing oxidative stress and autophagy.

Propyl gallate (PG), owing to its exceptional antioxidant properties, is extensively used in industries such as food processing. The potential harmful impacts of PG have sparked concern among people. It has been reported that exposure of PG has certain reproductive toxicity, which can affect the maturation of mouse oocytes and induce testicular dysfunction. However, its impact on early embryonic development is still unclear. In this study, we explored the toxic effects and potential mechanisms of PG on mouse 2-cell stage embryonic development. The results showed that exposure of PG can decrease the development of 2-cell stage embryos and repress the development of 4-cell stage embryos. Further study found that PG could induce intracellular oxidative stress and the accumulation of DNA damage in 2-cell stage embryos. Moreover, exposure of PG impaired the function of mitochondria and lysosomes in 2-cell stage embryos, thereby triggering the occurrence of autophagy. In addition, exposure of PG altered the epigenetic modification of 2-cell stage embryos, displaying a decreased level of DNA methylation and an increased level of H3K4me3. In summary, our results indicated that exposure of PG can damage the development of mouse 2-cell stage embryos by inducing oxidative stress, DNA damage, and autophagy, and altering epigenetic modification.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Curcumin alleviates bisphenol AF-induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway.

Bisphenol AF (BPAF), a BPA-substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl-2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF-induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen-activated protein kinase (MAPK) pathway and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF-induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

BACKGROUND: The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of non-classical 21-hydroxylase deficiency. For this study, we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature, which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia. METHODS: Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed. We examined the effects of gene mutations on protease activity and constructed three-dimensional structure prediction models of proteins. RESULTS: We describe 10 patients with 11beta-hydroxylase gene mutations (n = 5, 46,XY; n = 5, 46,XX), with 10 novel mutations were reported. Female patients received treatment at an early stage, with an average age of 2.08 ± 1.66 years, whereas male patients received treatment significantly later, at an average age of 9.77 ± 3.62 years. The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C > T. All mutations lead to spatial conformational changes that affect protein stability. CONCLUSIONS: Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations. Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations. The correlation between genotype and phenotype needs further study. Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

Chemical constituents from the roots of Dolomiaea souliei.

A new benzofuran-type neolignan (1), two new phenylpropanoids (2 - 3), and one new C21 steroid (4) were isolated from the ethyl acetate extract of the roots of Dolomiaea souliei by chromatographic methods, including silica gel, ODS column chromatography, MPLC, and semi-preparative HPLC. Their structures were identified as dolosougenin A (1), (S)-3-isopropylpentyl (E)-3-(4-hydroxy-3-methoxyphenyl) acrylate (2), (S)-3-isopropylpentyl (Z)-3-(4-hydroxy-3-methoxyphenyl) acrylate (3) and dolosoucin A (4) through various spectroscopic techniques including 1D NMR, 2D NMR, IR, UV, HR ESI MS, ORD, and computational ORD methods.

High-dose synthetic phenolic antioxidant propyl gallate impairs mouse oocyte meiotic maturation through inducing mitochondrial dysfunction and DNA damage.

Propyl gallate (PG) is one of the most widely used antioxidants in food products, cosmetics and pharmaceutical industries. Increased research has suggested that exposure to PG influences reproductive health in humans and animals. However, until now, it has not yet been confirmed whether PG would impact oocyte quality. In this study, the hazardous effects of PG on oocyte meiotic maturation were investigated in mice. The findings showed that PG exposure compromises oocyte meiosis by inducing mitochondrial stress which activates apoptosis to trigger oocyte demise. Moreover, DNA damage was significantly induced in PG-treated oocytes, which might be another cause of oocyte developmental arrest and degeneration. Besides, the level of histone methylation (H3K27me2 and H3K27me3) in oocyte was also significantly increased by PG exposure. Furthermore, PG-induced oxidative stress was validated by the increased level of reactive oxygen species (ROS), which might be the underlying reason for these abnormities. In conclusion, the foregoing findings suggested that PG exposure impaired oocyte meiotic maturation by yielding mitochondrial stress to activate apoptosis, inducing DNA damage and oxidative stress, and altering histone methylation level.

Gene Expression Network and Circ_0008012 Promote Progression in MLL/AF4 Positive Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia with MLL/AF4 rearrangement remains a major hurdle to improving outcomes. Gene network and circRNAs have been found to participate in tumorigenesis, while their roles in leukemia still need to be explored. Recent patents have shown that circRNAs exhibit the markers for the children ALL, although the target and related mechanism remain to be elucidated. OBJECTIVE: This study aims to explore the possible targets and mechanisms of ALL with MLLAF4 rearrangement. METHODS: We first generated a gene network focusing on MLL-AF4 rearrangement. Cell viability was determined with Cell Counting Kit-8 assay. The cell apoptosis was tested by the Annexin V/PI assay. The RNA-protein complexes were analyzed by qRT-PCR, and the pathway proteins were analyzed by western blot. RESULTS: This gene network was associated with biological processes, such as nucleic acid metabolism and immunity, indicating its key role in inflammation. We found that circ_0008012 was upregulated in MLL/AF4 ALL cells and regulated cell proliferation and apoptosis. Further computed simulation and RIP showed that IKKß was the strongest protein in the NF-κB pathway binding with circ_0008012. As a result, possible regulation of circ_0008012 is suggested by binding IKKß in the IKKα:IKKß:IKKγ compound, which then phosphorylates IκB and activates NF- κB:p65:p300 compound in cell nucleus, thereby leading to leukemia. CONCLUSION: We identified a gene network for MLL/AF4 ALL. Moreover, circ_0008012 may be a therapeutic target for this subtype of ALL.

Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes.

Introduction: The frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs. Materials and methods: Eighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected. Results: In total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb-) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb-:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10-6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb-:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells). Conclusion: This study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD.

Bromoacetic acid impairs mouse oocyte in vitro maturation through affecting cytoskeleton architecture and epigenetic modification.

As a major public health achievement, disinfection of drinking water significantly decreases outbreaks of waterborne disease, but produces drinking water disinfection by-products (DBPs) unfortunately. The haloacetic acids (HAAs) including bromoacetic acid (BAA), the second major class of DBPs, are considered as a global public health concern. BAA has been identified as cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic in somatic cells. However, the toxic effects of BAA on oocyte maturation remain obscure. Herein, we documented that exposure to BAA compromised mouse oocyte maturation in vitro, causing blocked polar body extrusion (PBE). Meiotic progression analysis demonstrated that exposure to BAA induced the activated spindle assembly checkpoint (SAC) mediated metaphase I (MI) arrest in oocytes. Further study revealed that exposure to BAA resulted in the hyperacetylation of α-tubulin, disrupting spindle assembly and chromosome alignment, which is responsible for the activation of SAC. Besides, the organization of actin, the other major component of cytoskeleton in oocytes, was disturbed after BAA exposure. In addition, exposure to BAA altered the status of histone H3 methylation and 5 mC, indicative of the damaged epigenetic modifications. Moreover, we found that exposure to BAA induced DNA damage in a dose-dependent manner in oocytes. Collectively, our study evidenced that exposure to BAA intervened mouse oocyte maturation via disrupting cytoskeletal dynamics, damaging epigenetic modifications and inducing accumulation of DNA damage.

[Systematic review and Meta-analysis of efficacy and safety of Biyuan Tongqiao Granules in treatment of chronic sinusitis].

The present study conducted a systematic review and Meta-analysis on the efficacy and safety of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science were searched for randomized controlled trials(RCTs) of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. The quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment tool and the final included trials underwent Meta-analysis with RevMan 5.4.1. Fifty-four RCTs were included, with a total sample size of 7 278 cases. The results of Meta-analysis showed that the clinical efficacy of Biyuan Tongqiao Granules alone or in combination in the experimental group in the treatment of chronic sinusitis was superior to that in the control group with conventional western medicine, Chinese medicinal preparations, or surgery only(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01). The combined use of Biyuan Tongqiao Granules on the basis of the control group was superior to the control group in improving the main symptoms and signs of chronic sinusitis [RR_(nasal congestion)=1.33, 95%CI[1.21, 1.45], P<0.000 01, RR_(runny nose)=1.28, 95%CI[1.18, 1.40], P<0.000 01, RR_(turbinate congestion or swelling)=1.28, 95%CI[1.16, 1.41], P<0.000 01]. Biyuan Tongqiao Granules alone or in combination could effectively reduce the Snot-20 score, which was superior to the control group(MD=-2.94, 95%CI[-3.60,-2.28], P<0.000 01). Biyuan Tongqiao Granules alone and in combination could effectively reduce the VAS score, which was superior to the control group(MD_(total score)=-4.44, 95%CI[-6.05,-2.82], P<0.000 01; MD_(nasal congestion VAS score)=-0.99, 95%CI[-1.38,-0.60], P<0.000 01; MD_(runny nose VAS score)=-1.19, 95%CI[-1.62,-0.76], P<0.000 01; MD_(dysosmia VAS score)=-0.96, 95%CI[-1.26,-0.65], P<0.000 01; MD_(head and face pain VAS score)=-0.73, 95%CI[-0.98,-0.47], P<0.000 01). The combined use of Biyuan Tongqiao Granules could effectively reduce the sinus CT score and the Lund-Mackey score of the endoscopic mucosal morphology(MD_(sinus CT score)=-3.68, 95%CI[-5.47,-1.88], P<0.000 1, MD_(endoscopic mucosal morphology score)=-3.06, 95%CI[-5.53,-0.59], P=0.02). Compared with the control group with conventional western medicine, Chinese medicinal preparations, or surgery only, combined use of Biyuan Tongqiao Granules did not increase the occurrence of adverse reactions(RR=0.68, 95%CI[0.26, 1.77], P=0.43). As demonstrated by the existing evidence, Biyuan Tongqiao Granules can improve the clinical efficacy of chronic sinusitis, relieve the clinical symptoms and signs, and reduce the Snot-20 score, VAS score, and Lund-Mackey score, without inducing serious adverse reactions, indicating that Biyuan Tongqiao Granules alone or in combination are more effective and safe in the treatment of chronic sinusitis than conventional western medicine, Chinese medicinal preparations, or surgical treatment. Since the quality of the included trials was generally low, large-scale, high-quality, rigorous, multi-center, and blinded-designed RCTs that meet international standards should be adopted in the future to increase the strength and level of evidence.

All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease.

Age-related neurodegenerative disorders such as Alzheimer's disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown that a variety of bioactive substances released by physical exercise (called "exerkines") help to maintain and improve the normal functions of the brain in terms of cognition, emotion, and psychomotor coordination. Increasing evidence suggests that exerkines may exert beneficial effects in AD as well. This review summarizes the neuroprotective effects of exerkines in AD, focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise. The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages, genders, and health conditions.

Selective EZH2 inhibitor zld1039 alleviates inflammation in cisplatin-induced acute kidney injury partially by enhancing RKIP and suppressing NF-κB p65 pathway.

Enhancer of zeste homolog 2 (EZH2), a component of polycomb repressive complex 2 (PRC2), is a histone lysine methyltransferase mediating trimethylation of histone H3 at lysine 27 (H3K27me3), which is a repressive marker at the transcriptional level. EZH2 sustains normal renal function and its overexpression has bad properties. Inhibition of EZH2 overexpression exerts protective effect against acute kidney injury (AKI). A small-molecule compound zld1039 has been developed as an efficient and selective EZH2 inhibitor. In this study, we evaluated the efficacy of zld1039 in the treatment of cisplatin-induced AKI in mice. Before injection of cisplatin (20 mg/kg, i.p.), mice were administered zld1039 (100, 200 mg/kg, i.g.) once, then in the following 3 days. We found that cisplatin-treated mice displayed serious AKI symptoms, evidenced by kidney dysfunction and kidney histological injury, accompanied by EZH2 upregulation in the nucleus of renal tubular epithelial cells. Administration of zld1039 dose-dependently alleviated renal dysfunction as well as the histological injury, inflammation and cell apoptosis in cisplatin-treated mice. We revealed that zld1039 administration exerted an anti-inflammatory effect in kidney of cisplatin-treated mice via H3K27me3 inhibition, raf kinase inhibitor protein (RKIP) upregulation and NF-κB p65 repression. In the cisplatin-treated mouse renal tubular epithelial (TCMK-1) cells, silencing of RKIP with siRNA did not abolish the anti-inflammatory effect of EZH2 inhibition, suggesting that RKIP was partially involved in the anti-inflammatory effect of zld1039. Collectively, EZH2 inhibition alleviates inflammation in cisplatin-induced mouse AKI via upregulating RKIP and blocking NF-κB p65 signaling in cisplatin-induced AKI. The potent and selective EZH2 inhibitor zld1039 has the potential as a promising agent for the treatment of AKI.

[Report standards for clinical comprehensive evaluation of Chinese patent medicine].

The clinical comprehensive evaluation of drugs is an important basis for the return of clinical value, decision-making of medical and health authorities, and allocation of medical resources. In July 2021, the National Health Commission issued the Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), which required the evaluation to be implemented from the six dimensions(safety, effectiveness, economy, innovation, suitability, and accessibility), and made detailed arrangements for the clinical comprehensive evaluation of drugs. As Chinese patent medicine differs from chemical medicines in terms of effective components and action modes, the clinical comprehensive evaluation of Chinese patent medicine should highlight the characteristics and advantages of traditional Chinese medicine(TCM) on the basis of general requirements of comprehensive clinical evaluation of drugs. At present, in the clinical comprehensive evaluation of Chinese patent medicine, unified report standards have not yet been generated, resulting in the uneven quality of existing reports. To standardize the clinical comprehensive evaluation report of Chinese patent medicine and improve its quality, the editorial team, based on the relevant policy documents of clinical comprehensive evaluation of drugs, formulated the clinical comprehensive evaluation report standards for Chinese patent medicine in combination with the previous practice and expert opinions. The report standards, containing seven sections with 15 items determined, focus on data source, evaluation content, evidence synthesis, quality control, and evaluation results supported with detailed interpretations to help researchers better understand and apply the report standards for clinical comprehensive evaluation of Chinese patent medicine, improve the report quality, and provide references for the decision-making by the national medical management authorities.

[Clinical comprehensive evaluation of Mudan Granules in treatment of diabetic peripheral neuropathy with Qi-deficiency and collateral stagnation syndrome].

This study explored the clinical comprehensive evaluation of Mudan Granules, aiming to promote the safe, effective and rational use of Mudan Granules, reflect its clinical value and provide a basis for medical decision-making. The safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine of Mudan Granules were combed, and the multi-criteria decision analysis(MCDA) model was used to carry out comprehensive evaluation on each dimension. In terms of safety, multiple sources of evidence showed that the adverse reactions of Mudan Granules mainly involved gastrointestinal system, with controllable safety risk rated as grade B. In terms of effectiveness, Mudan Granules can significantly alleviate the diabetic peripheral neuropathy(Qi-deficiency and collateral stagnation syndrome), limb and trunk numbness, pain and sensory abnormalities and other clinical symptoms, exhibiting positive curative effect rated as grade A. In terms of economy, Mudan Granules combined with Mecobalamin and other conventional western medicines is economical compared with the western medicine alone group, which is supported by sufficient evidence and clear results, rated as grade B. In terms of innovation, Mudan Granules is the only Chinese patent medicine with the indication of benefiting Qi for activating blood circulation and dredging collaterals in the Medicine Catalogue for National Basic Medical Insurance, Industrial Injury Insurance, and Maternity Insurance. It has important clinical innovation and is evaluated as grade A. In the aspect of suitability, Mudan Granules has good suitability in ADR treatment, drug characteristics and usage, and is rated as grade B. In terms of accessibility, Mudan Granules has the price level comparable to that of similar drugs, with good affordability. The resources of medicinal materials for the preparation of Mudan Granules are abundant and available, which is rated grade B. Moreover, Mudan Granules, as a hospital preparation with both functions of tonification and purgation, reflects the combination between syndrome differentiation and disease differentiation as well as the combination between overall and local characteristics, and has prominent Chinese medicine features. According to the above dimensions, we suggest to classify Mudan Granules as a class A preparation which can be directly included the policy results of basic clinical drug administration.

Blood Levels of Glycated Hemoglobin, D-Dimer, and Fibrinogen in Diabetic Retinopathy.

PURPOSE: This study aimed to describe the levels of glycated hemoglobin (HbA1c), D-dimer (D-D), and fibrinogen (FIB) in different types of diabetic retinopathy (DR). METHODS: A total of 61 patients with diabetes, who were treated in our department between November 2017 and May 2019, were selected. According to their non-mydriatic fundus photography and fundus angiography results, patients were divided into three groups, ie, the non-DR (NDR) group (n=23), the non-proliferative DR (NPDR) group (n=17), and the proliferative DR (PDR) group (n=21). A control group of 20 people who had tested negative for diabetes was also included. The levels of HbA1c, D-D, and FIB were measured and compared, respectively. RESULTS: The mean values of HbA1c were 6.8% (5.2%, 7.7%), 7.4% (5.8%, 9.0%), and 8.5% (6.3%, 9.7%) in the NDR, NPDR, and PDR groups, respectively. The control group values were 4.9% (4.1%, 5.8%). These results indicated a significant statistical difference between groups. The mean values of D-D were 0.39 ± 0.21 mg/L, 1.06 ± 0.54 mg/L, and 1.39 ± 0.59 mg/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 0.36 ± 0.17 mg/L. The values of the NPDR and PDR groups were significantly higher than those of the NDR and control groups, and the value of the PDR group was significantly higher than that of the NPDR group, indicating a significant difference between the groups (P < 0.001). The mean values of FIB were 3.07 ± 0.42 g/L, 4.38 ± 0.54 g/L, and 4.46 ± 1.09 g/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 2.97 ± 0.67 g/L. The difference between the groups was statistically significant (P < 0.05). CONCLUSION: Blood levels of HbA1c, D-D, and FIB in the PDR group were significantly higher than in the NPDR group.

[Systematic evaluation and Meta-analysis on effectiveness and safety of Yupingfeng Granules on recurrent respiratory tract infection].

To evaluate the effectiveness and safety of Yupingfeng Granules in the treatment of recurrent respiratory tract infection.Six Chinese and English databases were retrieved,namely CNKI,Wan Fang,VIP,CBM,PubMed and Cochrane Library. Randomized controlled trials of Yupingfeng Granules in the treatment of recurrent respiratory tract infection were collected and screened. According to the evaluation criteria and tools of Cochrane,the heterogeneity among the studies was analyzed,and the Meta-analysis was carried out by Rev Man 5.3 software. A total of 16 studies were included in this study,with a total sample size of 1 788 cases,including 901 cases in the experimental group and 887 cases in the control group. Among them,11 intervention measures were Yupingfeng Granules combined with Western medicine routine vs routine Western medicine,and 5 research interventions were Yupingfeng Granules combined with pidomod vs pidomod based on routine therapy. Meta-analysis showed that the total effective rate of Yupingfeng Granules combined with Western medicine in the treatment of recurrent respiratory tract infection was better than that of Western medicine( RR= 1. 27,95%CI[1. 21,1. 34],P<0. 000 01). Based on the routine therapy,the total effective rate of Yupingfeng Granules combined with pidomod in the treatment of recurrent respiratory tract infection was better than that of pidomod( RR = 1. 23,95% CI[1. 13,1. 35],P<0. 000 01). A total of 21 cases of adverse events were reported in this study,including 6 cases in the experimental groups combined with traditional Yupingfeng Granules therapy and conventional Western medicine therapy and 15 in the control group. The adverse events were mainly gastrointestinal reactions,such as fatigue,nausea and diarrhea,which can tolerate or disappear with no impact on treatment. The incidence of adverse events in the two groups was not statistically significant( RR = 0. 44,95% CI[0. 19,1. 03],P = 0. 06). The results showed no significant difference in the incidence of adverse events between the two groups during treatment. Based on the routine therapy,no adverse event was reported in Yupingfeng Granules pidomod vs pidomod,indicating that both groups were safe. The analysis showed that Yupingfeng Granules combined with routine Western medicine therapy or combined with pidomod could increase the level of immunoglobulin and T lymphocytes in children. Based on the existing data and methods,Yupingfeng Granules combined with routine Western medicine therapy for recurrent respiratory tract infection can improve the total effective rate,immune function and body immunity,with no serious adverse reaction. However,because of the low quality of the literatures included in this study,it is still necessary to adopt well-designed large-sample clinical trials in conformity to international standards to improve the quality of evidence.