The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Objective To investigate the efficacy and safety of subcutaneous immunotherapy(SCIT)using dust mites in children with allergic asthma.Methods In a prospective randomized controlled study,98 children with dust mite-induced allergic asthma were randomly divided into a control group(n=49)and an SCIT group(n=49).The control group received inhaled corticosteroid treatment,while the SCIT group additionally received a standardized three-year SCIT regimen.The two groups were compared based on peripheral blood eosinophil percentage,visual analogue score(VAS),total medication score,Asthma Control Test/Childhood Asthma Control Test scores,fractional exhaled nitric oxide(FeNO),and lung function before treatment,and at 6 months,1 year,2 years,and 3 years after treatment.Adverse reactions were recorded post-injection to evaluate the safety of SCIT.Results Compared with pre-treatment levels,the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils,VAS,total medication score,and FeNO,while lung function significantly improved,and asthma control levels were better 3 years after treatment(P<0.05).Compared with the control group,the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment(P<0.05).A total of 2 744 injections were administered,resulting in 157 cases(5.72%)of local adverse reactions and 4 cases(0.15%)of systemic adverse reactions,with no severe systemic adverse events.Conclusions SCIT is an effective and safe treatment for allergic asthma in children.

Objective:To construct an evaluation index system of internal control medical equipment based on the internal control theory of The Committee of Sponsoring Organizations of the Treadway Commission(COSO)and combined with the current situation of medical equipment internal management in public hospitals,so as to provide reference and suggestions for the evaluation of internal control of medical equipment in public hospitals.Methods:Through literature research and expert consultation,the evaluation index system of internal control of medical equipment was preliminarily determined.Using the Delphi method,15 experts from 1 medical college and 3 tertiary hospitals in Beijing who were engaged in the use and management of medical equipment were selected to conduct two rounds of consultation on the evaluation index system of internal control of medical equipment,and the evaluation indicators were scored and screened.The analytic hierarchy process(AHP)was used to determine the index weights,and the internal control evaluation index system of medical equipment in public hospitals based on COSO was constructed.Results:The coefficient of the two rounds of expert consultation was 100%.The authority degree of consulting experts was 0.867.Finally,the evaluation index system of internal control of medical equipment in tertiary public hospitals was formed,which included 5 first-level indicators,17 second-level indicators and 50 third-level indicators.Conclusion:The evaluation index of internal control of medical equipment in public hospitals based on COSO has high expert enthusiasm,authority and coordination.The evaluation index system includes the unit level and the business level of internal control,with a wide coverage,which makes up for the limitations of traditional internal evaluation of medical equipment,which can make up for the limitations of the internal evaluation of traditional medical equipment,improve the internal control system of medical equipment in public hospitals,and optimize the medical equipment management system.

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

OBJECTIVE: To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine. METHODS: Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups. RESULTS: The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients. CONCLUSION Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.
Humans ; Electroacupuncture ; Aquaporin 4 ; Acupuncture Therapy ; Cerebral Hemorrhage/therapy* ; Treatment Outcome ; Acupuncture Points

OBJECTIVE: To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD). METHODS: A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24⁺), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24⁺) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups. RESULTS: After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups (P<0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group (P<0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group (P<0.05). CONCLUSION Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.
Humans ; Sertraline/adverse effects* ; Depression/etiology* ; Acupuncture Therapy ; Electroacupuncture ; Stroke/complications* ; Acupuncture Points ; Treatment Outcome ; Tablets

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

OBJECTIVE: To build bridges between anti-α enolase antibody (anti-enolase 1 antibody, anti-ENO1 antibody) and common clinical and laboratory characteristics of systemic lupus erythematosus (SLE) and to analyze the role of anti-ENO1 antibody in the evaluation of SLE disease activity. METHODS: The SLE patients with retinopathy and without retinopathy were enrolled in the study, as well as healthy individuals whose gender and age matched with those of the SLE patients. Serum anti-ENO1 antibodies were measured using enzyme-linked immunosorbent assay (ELISA), presenting as intra-group positive rate and arbitrary units (AU) value. Clinical and laboratory data were obtained from medical records. RESULTS: The SLE retinopathy patients represented various fundus abnormalities. Ranked by percentage, the top three retinopathies were retinal hemorrhage (14/32, 43.75%), cotton-wool spots (8/32, 25.00%) and retinal vein occlusion (3/32, 9.38%). Among the 32 SLE retinopathy patients, 13 (40.63%) suffered from two or more fundus abnormalities. The positive rate and AU value of the SLE patients were higher than of the SLE patients without retinopathy (68.75% vs. 46.00%, P=0.043; 16.11%±10.35% vs. 12.06%±6.47%, P=0.045). Besides, the positive rate and AU value of the two SLE groups were both significantly higher than those of the healthy control group (P < 0.001). Compared with the SLE-without-retinopathy group, the systemic lupus erythematosus disease activity index (SLEDAI)-2000 of the SLE retinopathy patients were significantly higher than those of the SLE patients without retinopathy (17.41±4.25 vs. 9.48±5.35, P < 0.001). Dividing all the SLE patients into an anti-ENO1-positive group and an anti-ENO1-negative group, we found that anti-ENO1-positive was more likely to be correlated to developing fever and positive result of urine occult blood (P=0.011, P=0.042). Comparing with the patients with negative anti-ENO1 antibodies, the patients with positive anti-ENO1 antibodies had significantly higher erythrocyte sedimentation rate (ESR) [the median (range) was 29.50 (1.52-110.00) mg/L vs. 12.00 (4.00-101.00) mg/L, P=0.001], higher immunoglobulin G (IgG) [the median (range) was 14.30 (4.02-37.80) g/L vs. 10.46 (2.50-25.73) g/L, P=0.000 3], and higher blood platelet count (PLT) [(205.87×10⁹±67.98×10⁹) /L vs. (164.57×10⁹±69.57×10⁹) /L, P=0.008], as well as higher immunoglobulin A (IgA) [the median (range) was 2.85 (0.07-27.00) g/L vs. 2.05 (0.42-4.36) g/L, P=0.014]. CONCLUSION The positive rate and AU value of anti-ENO1 antibody suggested higher SLE disease activity and they were elevated in SLE and SLE retinopathy.
Humans ; Autoantibodies ; Lupus Erythematosus, Systemic ; Enzyme-Linked Immunosorbent Assay ; Retinal Diseases/etiology* ; Immunoglobulin G