Objective To observe the effect of dulaglutide combined with insulin aspart and metformin on blood glucose,pancreatic beta-cell status and physique in elderly patients with type 2 diabetes mellitus(T2DM)and obesity.Methods Elderly patients with T2DM and obesity were divided into the control group and the treatment group according to the queue method.Both groups were given intensive insulin therapy with insulin aspart injection at 0.4-0.6 U·kg-1·d-1 and oral administration of 0.5 g of metformin tablets,tid.A week later,the treatment of control group was switched to sequential therapy with insulin glargine injection at an initial dose of 0.4-0.6 U·kg-1·d-1,qn.The dose was adjusted according to blood glucose concentration.During this period,0.5 g of metformin tablets was administrated,tid,for 12 consecutive weeks.Meanwhile,treatment of the treatment group was switched to sequential therapy with 1.5 mg of dulaglutide injection,once a week.During this period,0.5 g of metformin tablets was administrated,tid,for 12 consecutive weeks.The two groups were compared in terms of clinical efficacy,blood glucose level[glycosylated hemoglobin(HbAlc),fasting plasma glucose(FPG)],pancreatic beta-cell status[fasting insulin(FINS),homeostasis model assessment-β(HOMA-β)and homeostasis model assessment-insulin resistance index(HOMA-IR)],and physical parameters[waist circumference and body mass index(BMI)].Safety was evaluated.Results Fifty-three cases and fifty-one cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 98.11％(52 cases/53 cases)and 84.31％(43 cases/51 cases),and the difference was statistically significant(P＜0.05).After treatment,HbAlc in the treatment and the control group were(7.01±0.75)％and(7.63±0.82)％;FPG levels were(6.23±0.70)and(6.62±0.74)mmol·L-1;FINS levels were(5.25±1.06)and(6.48±1.12)mU·L-1;HOMA-β were 32.62±6.53 and 27.19±5.18;HOMA-IR were 1.31±0.25 and 1.65±0.28;waist circumference were(82.31±6.04)and(85.79±6.82)cm;BMI were(27.14±1.23)and(27.91±1.15)kg·m-2.The differences in above indicators between the treatment group and the control group were statistically significant(all P＜0.05).Adverse drug reactions in the treatment group mainly included nausea,vomiting and skin rash.Adverse drug reactions in the control group mainly included nausea and vomiting.The total incidence rates of adverse drug reactions in the treatment and the control group were 11.32％and 9.80％,without statistically significant difference(P＞0.05).Conclusion Dulaglutide combined with insulin aspart and metformin can effectively improve blood glucose,lipids,inflammation and pancreatic β-cell status in elderly patients with T2DM and obesity,reduce glycemic excursions,and promote decreases in waist circumference and BMI,with good safety.

This study was aimed at analyzing the clinical and laboratory characteristics of patients with Listeria monocyto-genes bacteremia,to provide evidence for its diagnosis and treatment.A retrospective analysis was conducted on the clinical data for patients with L.monocytogenes bacteremia at Tangdu Hospital between September 2012 and April 2022.The data included age,sex,underlying diseases,treatments,and prognosis.Changes in indicators such as white blood cell(WBC)count,mono-cyte percentage,neutrophil percentage,monocyte/neutrophil ratio(M/N),C-reactive protein(CRP),and procalcitonin before and after treatment were statistically analyzed.Among the 32 patients with L.monocytogenes bacteremia,the average age was 31.9 years,and three patients were older than 65 years.The incidence rate was highest in summer(11 patients,34.4％),fol-lowed by spring(9 patients,28.1％).A total of 24 patients(75.0％)had underlying diseases.After accurate diagnosis,the treatment plans of 29 patients were adjusted to target antibacterial therapy consisting primarily of penicillins(17 patients,53.1％)and carbapenems(12 patients,37.5％).After treatment,the levels of neutrophils,lymphocytes,and CRP were signifi-cantly lower than those before treatment(P＜0.05).A total of 29 patients(90.6％)improved and were discharged,one patient died,and two patients had poor prognosis.The primary risk factors for L.monocytogenes infection were autoimmune diseases,tumors,and pregnancy.Penicillin was the first choice effective empirical treatment for listeriosis.A clear diagnosis of the pathogen and appropriate choice of antibiotics were particularly important for the treatment of L.monocytogenes infection.

Objective:To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies,in order to provide reference for clinical infection control and treatment.Methods:The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed.They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation.The types of pathogens and their drug resistance were analyzed.Results:Two hundred and ninety-nine positive strains of pathogenic bacteria were detected.In the transplantation group,Gram-negative bacteria accounted for 68.5％(50/73),Gram-positive bacteria accounted for 6.8％(5/73),and fungi accounted for 24.7％(18/73).The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8％,and 11.5％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0％,and 56.2％to carbapenems.In the non-transplantation group,Gram-negative bacteria accounted for 64.1％(145/226),Gram-positive bacteria accounted for 31.0％(70/226),and fungi accounted for 4.9％(11/226).Gram-positive bacteria were mainly Enterococcus faecium(6.6％,15/226)and Coagulase-negative Staphylococci(6.2％,14/226).The fungi were all Candida tropicalis.The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8％,and 10.3％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3％,and 26.8％to carbapenems.Conclusion:The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied.Gram-negative bacteria is the main pathogenic bacteria.The resistance of pathogenic bacteria to antibiotics is severe.Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To investigate the detection rate of pulmonary nodules (PN) by CT scan at different doses and the application value of artificial intelligence(AI) system assistance.Methods:From October 2019 to October 2021, 210 patients with PN in Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, were retrospectively selected, and they were divided into the study group (106 cases) and the control group (104 cases) by CT scan at different doses. The control group used the conventional average dose (169 mAs) CT scan, the study group used an average low-dose (54 mAs) CT scan. The PN detection rate of different gender, age, body mass index (BMI) between the two groups were compared. The morphological characteristics, radiation dose, CT image quality between the two groups were compared. The diagnostic efficiency of radiologists and AI system was compared.Results:The detection rate of PN in the study group and the control group had no significant difference: 73.58% (78/106) vs. 80.77%(84/104), χ2 = 1.54, P>0.05. The detection rate of PN with different gender, age group and BMI in the two groups had no significant differences ( P>0.05). The diameter of nodules and the rates of calcification, cavitation, bronchial sign, lobar sign, burr sign and pleural adhesion sign in the two groups had no significant differences ( P>0.05). The mean effective tubular bulb dose, length product of radiation dose, total tubular bulb dose, radiation volume dose index in the study group were higher than those in the control group: (46.15 ± 7.38) mAs vs. (104.39 ± 10.53) mAs, (169.24 ± 19.77) mGy·cm vs. (427.17 ± 43.58) mGy·cm, (972.65 ± 58.34) mAs vs. (2 861.26 ± 181.37) mAs, (3.55 ± 1.16) mGy vs. (8.95 ± 2.07) mGy, there were statistical differences ( P<0.05). The excellent, good, acceptable, poor of 1.0 mm image quality in the study group were 26, 60, 18, 2, and in the control group were 32, 64, 8, 0, there was statistical difference ( u =1.71, P = 0.087). The excellent, good, acceptable, poor of maximum intensity projection (MIP) image quality in the study group were 58, 42, 6, 0 and in the control group were 70, 34, 0, 0, there was statistical difference ( u = 1.81, P = 0.070). The detection rate of PN by AI low-dose CT scan was higher than that of radiologists: 88.68%(94/106) vs. 73.58%(78/106), there was statistical difference ( χ2 = 7.89, P = 0.005). Conclusions:The low-dose CT chest scans for PN, the results of detection rate, morphological characteristics, CT image quality are basically the same as those of conventional-dose CT chest scans, and can greatly reduce the radiation dose, which is more suitable for PN screening, and combined with AI system can significantly improve the detection rate of PN.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L^-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min^-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL^-1 (r = 1.000 0), 0.244-9.75 µg·mL^-1 (r = 0.999 9), 0.244-4.80 µg·mL^-1 (r = 0.999 9), 0.254-1.02 µg·mL^-1 (r = 0.999 9), and 0.247-0.987 µg·mL^-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL^-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.

Abstract: Objective　To analyze the serotype distribution, drug resistance rate and drug resistance gene carrying of Streptococcus pneumoniae isolates in hospitalized patients, and evaluate the coverage of the vaccine to the serotype of Streptococcus pneumoniae in this area, so as to provide reference for the rational use of antibiotics in clinic. Methods　A total of 150 strains of non-repetitive Streptococcus pneumoniae isolated from inpatients from January 2015 to December 2019 were collected for serotyping and antimicrobial sensitivity test. The carrying rates of pbp2b, ermB and tetM were detected by PCR. Results　The PCR classification rate of 150 strains of Streptococcus pneumoniae was 93.1%, and the classification rate of capsular swelling test was 100%, and a total of 19 serotypes were divided, mainly 19F and 6B. Children's serotypes were predominantly 19F, 6B, and 15A; adult serotypes were predominantly 19F, 14, and 23F. The coverage rates of the PCV7, PCV10, PCV13 and PPV23 vaccines were 36.8%, 42.1%, 57.9% and 68.4%, respectively. Strains with serotypes of 19F, 6B, 3, and 23F had higher rates of resistance to antimicrobials. The sensitivity of Streptococcus pneumoniae to penicillin was greater than 96.0%. Antimicrobials with significant differences in resistance rates between invasive and non-invasive strains were penicillin, moxifloxacin, and levofloxacin. The percentage of strains carrying both ermB and tetM resistance genes was 96.0%, and the concordance rate between pbp2b, ermB and tetM resistance genes and the resistance phenotype was >98.0%. A total of 10 multi-resistance combinations were detected, with a multi-resistance rate of 62.6%, and the multi-drug resistance pattern of Streptococcus pneumoniae was mainly concentrated in the 19F and 6B serotypes. Conclusion　There are significant age differences in the serotypes of Streptococcus pneumoniae in this area. The vaccine currently used has low coverage in this region and therefore offer limited protection to the population. The drug resistance rates of Streptococcus pneumoniae varied significantly among serotypes. Erythromycin and tetracycline are not recommended for clinical treatment of Streptococcus pneumoniae. Penicillin can still be used as the first choice for clinical treatment of Streptococcus pneumoniae infection.