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.

Objective:To systematically screen and identify long noncoding RNA(lncRNA)associated with bone marrow adiposity changes in aplastic anemia(AA).Methods:The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened.The expression of candidate lncRNA was verified by qRT-PCR in the in vitro adipogenic differentiation model of BM-MSC,BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls.Results:PPARγ and C/EBPα were significantly highly expressed in AA BM-MSC,and knock-down of PPARγ and C/EBPα impaired the adipogenic capacity of AA BM-MSC.PPARγ and C/EBPα cotranscriptionally activate LINC01230 promoter activity in binding sites dependant manner.The LINC01230 was also aberrantly highly expressed in AA BM-MSC compared with controls.Conclusion:PPARγ and C/EBPα are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC,and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating LINC01230 expression.

Cardiovascular disease is a major threat to human health and has become the leading cause of death worldwide; therefore, early diagnosis and treatment are of great value. Due to its miniaturization, integration, and ease of operation, microfluidic technology enables the rapid, multi-target detection of cardiovascular disease markers and significantly facilitates the early and rapid diagnosis of cardiovascular disease. This article reviews the research progress of microfluidics in cardiovascular disease detection, analyzes its advantages and weaknesses in the rapid detection of protein, lipid, and nucleic acid biomarkers, hopes to provide a reference to promote the quick detection technology of cardiovascular disease, and thus proposes new considerations for the early management of cardiovascular disease.
Humans ; Microfluidics ; Cardiovascular Diseases/diagnosis* ; Biomarkers ; Early Diagnosis

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.

Celastrol, extracted from Tripterygium wilfordii, is a natural pentacyclic triterpene compound, which has an anti-pulmonary fibrosis effect. However, its effect, binding targets and regulatory mechanism in pulmonary fibroblasts remain unclear. In this study, we found that celastrol could prevent fibroblast-myofibroblast transformation (FMT) by significantly inhibiting transforming growth factor β1 (TGFβ1)-induced α-smooth muscle actin and type I collagen expression. Previous studies suggested that heat shock protein 60 (HSP60) may be the target of celastrol. This study confirmed the direct interaction between celastrol and HSP60 through cellular thermal shift assay and surface plasmon resonance experiment, and demonstrated that the K_D value of celastrol binding to HSP60 was 8.59 μmol·L^-1. Further studies showed that knockdown of HSP60 promoted TGFβ1-induced FMT, especially in the medium and low dose TGFβ1 treatment group, and that the anti-FMT effect of celastrol was significantly weakened after HSP60 knockdown. These results indicated that HSP60 was involved in maintaining the resting state of fibroblasts, and the anti-FMT effect of celastrol was dependent on HSP60. Furthermore, the autophagy promotion and antioxidant effects of celastrol were also weakened after HSP60 knockdown. In conclusion, celastrol inhibits FMT by targeting HSP60, thus exerting anti-pulmonary fibrosis function.

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

OBJECTIVE To establish characteristic HPLC chromatograms for Jubei mixture, and to simultaneous determine its six components by HPLC-ELSD. METHODS An HPLC specific chromatogram of the Jubei mixture was established. The chromatographic column was Agilent ZORBAX-C18(250 mm×4.6 mm, 5 μm), gradient elution was conducted with acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) as the mobile phase, the flow rate was 1.0 mL·min-1, and the column temperature was 30℃, the detection wavelength was 250 nm. An HPLC-ELSD method was established and the chromatography was accomplished on a Waters T3 C18(250 mm×4.6 mm, 5 μm) column, the mobile phase consisted of acetonitrile(A)-1% acetic acid aqueous solution(B) in a gradient mode, the flow rate was 1.0 mL·min-1, the column temperature was set at 30℃. RESULTS The characteristic chromatograms of the HPLC with baicalin as the reference peak was established, and eight common peaks were defined. The linear ranges of amygdalin, liquiritin, peimine, peiminine, platycodin D and ophiopogonin D were good within their own ranges(r ≥ 0.999). The average recovery were 99.1%, 98.6%, 100.9%, 97.7%, 98.9% and 98.0%, RSD were 0.4%, 1.0%, 1.1%, 1.2%, 0.7% and 1.3%, respectively. CONCLUSION The established methods can be used to qualitative identification and quantitative determination of Jubei mixture, can effectively used for evaluation and quality control of Jubei mixture.

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition.Moreover, EVs decreased the lipid accumulation rate during adipogenic induction.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors