Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

Objective To investigate the effect of XUE Ji's morning-evening supplementing method,a therapy by tonification according to the alteration of daily yang-qi in the human body and the nature proposed by practitioner XUE Ji in Ming Dynasty,combined with Seretide on exercise endurance in patients with stable chronic obstructive pulmonary disease(COPD)of lung and kidney deficiency type.Methods Ninety-two patients with stable COPD of lung and kidney deficiency type were randomly divided into treatment group and control group,with 46 cases in each group.The control group was given inhalation of Salmeterol/Fluticasone Inhalation Powder(Seretide),and the treatment group was treated with Buzhong Yiqi Pills in the morning and Liuwei Dihuang Pills at evening on the basis treatment for the control group.The course of treatment covered 3 months.The changes of the scale scores of traditional Chinese medicine(TCM)syndrome and St Georges respiratory questionnaire(SGRQ)for quality of life,the distance of 6-minute walking test(6MWT)for exercise endurance,and pulmonary function indicators of forced expiratory volume in one second(FEV1),forced vital capacity(FVC)and their ratio(FEV1/FVC)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)During the trial,a total of 3 cases were lost,and a total of 89 patients were eventually included,including 45 cases in the treatment group and 44 cases in the control group.(2)After 3 months of treatment,the total effective rate of the treatment group was 82.22％(37/45),and that of the control group was 72.73％(32/44).The intergroup comparison by chi-square test showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the scores of TCM syndromes in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease in the treatment group was more significant than that in the control group(P＜0.01).(4)After treatment,the lung function indicators of FEV1,FVC and FEV1/FVC in the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the scores of SGRQ items of respiratory symptoms,disease impact and activity limitation in the two groups were significantly lower than those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P＜0.01).(6)After treatment,the 6MWT distance of the two groups was significantly improved compared with that before treatment(P＜0.01),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.01).(7)During the treatment,no abnormal changes in the indicators of blood routine test,liver and kidney function,electrocardiogram,and urine and stool routine were found in the two groups.Conclusion XUE Ji's morning-evening supplementing method combined with Seretide exert certain effect in treating stable COPD patients with lung and kidney deficiency syndrome.The therapy can effectively alleviate the clinical symptoms ofnd improve the lung function,exercise endurance and quality of life of the patients,with high safety.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Objective: To systematically evaluate the factors affecting diabetic retinopathy (DR) among Chinese adult patients with type 2 diabetes mellitus (T2DM), so as to provide insights into establishment of personalized risk prediction models for DR. Methods: Case-control studies pertaining to factors affecting DR among Chinese adults were retrieved from international and national databases, including CNKI, Wanfang Data, SinoMed, PubMed, Web of Science, Embase and CINAHL from inception to March 31, 2023. A meta-analysis was performed using the software Stata 17.0, and subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was performed using the leave-one-out method, and the publication bias was evaluated using the Egger's test and trim-and-fill method. Results: Totally 4 969 publications were retrieved, and 35 case-control studies were finally enrolled, including 32 high-quality publications (91.43%). The included studies involved 29 228 participants and 10 568 DR patients, and the prevalence of DR was 36.16%. Meta-analysis revealed that age (OR=1.06, 95%CI: 1.00-1.13), duration of T2DM (OR=1.09, 95%CI: 1.08-1.11), systolic blood pressure (OR=1.02, 95%CI: 1.01-1.03), glycated hemoglobin A1c (OR=1.38, 95%CI: 1.26-1.50), fasting blood glucose (OR=1.57, 95%CI: 1.07-2.31), urinary albumin to creatinine ratio (OR=1.50, 95%CI: 1.10-2.04), serum uric acid (OR=1.01, 95%CI: 1.00-1.01), urine microprotein (OR=2.01, 95%CI: 1.96-2.07), triglyceride (OR=1.77, 95%CI: 1.42-2.21), and total cholesterol (OR=1.82, 95%CI: 1.50-2.21) were risk factors for DR, and glomerular filtration rate (OR=0.98, 95%CI: 0.97-0.98) and C-peptide (OR=0.79, 95%CI: 0.68-0.93) were protective factors for DR. Sensitivity analysis of age effects was not robust. Following adjustment for glomerular filtration rate with the trim-and-fill method, there was still a publication bias, and the publication bias of other influencing factors had no impact on pooled effects. Conclusions Age, course of T2DM, systolic blood pressure, glycated hemoglobin A1c, fasting blood glucose, urinary albumin to creatinine ratio, serum uric acid, urine microprotein, triglyceride and total cholesterol were risk factors, and glomerular filtration rate and C-peptide were protective factors for DR among Chinese adults.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.
Rats ; Female ; Animals ; Rats, Sprague-Dawley ; Network Pharmacology ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Kidney ; Arginine ; Water

OBJECTIVE: To explore clinical efficacy of dorsal plate assisted fixation of dorsal lunate fossa fracture block of distal radius. METHODS: From January 2019 to January 2022, 30 patients were treated with dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius, including 13 males and 17 females, aged from 42 to 68 years old with an average of (48.7±5.6) years old;According to Doi fracture classification, 24 patients were type 3 blocks and 6 patients were type 4 blocks. The degree of palmar angle of anterior and posterior distal radius was fixed by dorsal steel plate during operation. Fracture healing and functional recovery of wrist were observed after operation. Functional evaluation was performed by Gartland and Werley scoring system at 12 months after operation. RESULTS: All patients were followed up from 12 to 13 months with an average of (11.3±0.9) months. All fractures healed for 4 to 5 months with an average of(4.7±0.8) months. Median palpal inclination of anterior and posterior distal radius fixed by dorsal plate was 5.30°(4.85°, 6.03°), 12.45°(11.98°, 13.43°) respectively, and had statistical difference( P<0.01). Gartland and Werley scores was (1.1±0.4) at 12 months afteropertaion, and 27 patients got excellent result and 3 good. CONCLUSION Dorsal plate assisted fixation of dorsal lunate fossa fractures is beneficial to reduction and stabilization of displaced dorsal fractures and restoration of palmar inclination.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Radius/surgery* ; Lunate Bone/surgery* ; Upper Extremity ; Wrist Joint ; Wrist ; Fractures, Bone

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.