OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective: To analyze the effects of community-based interventions for diabetic eye diseases in Xinjing community, Shanghai from 2016 to 2018. Methods: Based on the project of "Establishment of Service Model for Comprehensive Prevention and Treatment of Diabetic Eye Diseases in Shanghai", the participants were not suffering diabetic retinopathy (DR) in Xinjing community in 2016 before interventions and received community-based interventions for diabetic eye diseases. The incidence of DR, visual acuity and awareness of DR were used as evaluation indicators to analyze the effects of interventions for diabetic eye diseases in the community. Results: A total of 537 patients were included in this study, the incidence of DR among diabetic patients in Xinjing community was 7.6% after interventions. The duration of diabetes (OR= 1.065) and HbA1c (OR= 1.090) were the risk factors of DR. Before and after the interventions, the patients with monocular low vision and binocular low vision were 27 cases (5.0%), 8 cases (1.5%), 19 cases (3.5%) and 7 cases (1.3%) respectively. After interventions, the awareness on the prevention and treatment of DR increased significantly, and the proportion of regular visits to ophthalmology examination, diet control and physical exercise also increased significantly. Conclusion: Community-based interventions for diabetic eye diseases are helpful to improve the awareness of DR prevention and control, reduce the incidence of DR.
China/epidemiology* ; Cross-Sectional Studies ; Diabetes Mellitus ; Diabetic Retinopathy/prevention & control* ; Exercise ; Humans ; Risk Factors

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; Chemotherapy, Adjuvant ; Cross-Sectional Studies ; Female ; Gastrointestinal Stromal Tumors/drug therapy* ; Humans ; Imatinib Mesylate/therapeutic use* ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy*

The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.
Acetaminophen/toxicity* ; Alanine Transaminase/metabolism* ; Animals ; Aspartate Aminotransferases/metabolism* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Liver/enzymology* ; Malondialdehyde/analysis* ; Mice ; Oxidative Stress ; Plant Extracts/pharmacology* ; Superoxide Dismutase/metabolism*

【Objective】 To investigate the function and molecular mechanism of osteosarcoma cells derived exosome on microenvironment of target organs. 【Methods】 The osteosarcoma derived exosomes were extracted and injected into nude mice through tail vein after PKH26 fluorescence staining. The liver, spleen, lung, kidney and brain tissues were extracted 24 hours later and then the amount of red fluorescence in different fields was counted under fluorescence microscope. The uptake of exosomes in different types of cells was detected by immunofluorescence. 143B derived exosomes were co-cultured with human lung fibroblasts, and the uptake was detected by fluorescence microscopy. The expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were detected by RT-qPCR, while the changes of p-p65 in inflammatory signaling pathway of NF- κB and p-ERK, p-p38 in MAPK signaling were detected by western blotting. 【Results】 TSG101, Flotillin-1, CD63 and CD9 were expressed in 143B derived exosomes, and Calnexin expression was absent(P<0.05). The exosomes presented a saucer-like structure under electron microscope. The size of the exosomes is(141.92± 52.85) nm. The exosomes distributed more in lung tissue than liver, kidney, spleen and brain after injection through the tail vein of nude mice(P<0.05). The mRNA levels of inflammatory cytokines IL-1β, IL-6and TNF-α were significantly increased in human lung fibroblast cells after incubation with 143B exosomes(P<0.05). p-p65, p-ERK and p-p38MAPK were significantly up-regulated(P<0.05) . 【Conclusions】 Osteosarcoma cells derived exosomes could activate inflammatory signaling pathway NF-κB and MAPK, and up-regulate the expression of the inflammatory cytokines IL-1β, IL-6 and TNF-α in lung fibroblast cells.

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.
Animals ; Cytokines ; Gastric Mucosa ; Indomethacin ; Omeprazole ; pharmacology ; Phytochemicals ; pharmacology ; Random Allocation ; Rats ; Rosaceae ; chemistry ; Stomach Ulcer ; chemically induced ; drug therapy ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha

To observe the effect of total triterpenoids of Chaenomeles speciosa on PPARγ/SIRT1/NF-κBp65 signaling pathway and intestinal mucosal barrier of ulcerative colitis induced by dextran sulfate sodium (DSS) in mice, C57BL/6 mice were randomly divided into normal group, model group, total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) groups and sulfasalazine (250 mg·kg⁻¹) group. The ulcerative colitis (UC) model was induced by orally administering 2.5% DSS to the experimental mice, and the corresponding drugs were given to each group 3 days before the administration with 2.5% DSS. The normal group and the model group were given the equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage continuously for 10 days, q.d. The general conditions of the mice were observed on a daily basis, and the disease activity index (DAI) score was recorded. On the 10th day after the treatment, mice were put to death, the contents of TNF-α, IL-1β, IL-6, IFN-γ, IL-4 and IL-10 in the blood were detected, colon length was measured, colon mucosa damage index (CMDI) score was calculated, and MPO activity detection and histomorphology analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of E-cadherin, occluding,MUC2 and TFF3; the protein expressions of SIRT1, IKKβ, p-IKKβ, IκBα, p-IκBα and cytosol and nucleus PPARγ, NF-κBp65 in intestinal tissue were detected by western blot. The results indicated that total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) could significantly improve the general conditions of UC mice, reduce the DAI, CMDI and histopathological scores, increase the colon length, reduce the colonic mucosa ulcers, erosion and inflammatory infiltration, restore the normal intestinal mucosal barrier function, reduce the contents of TNF-α, IL-1β, IL-6, IFN-γ, increase the contents of IL-4 and IL-10 in the blood, inhibit MPO activity in colon tissue, up-regulate the mRNA expressions of E-cadherin, occludin, MUC2 and TFF3 in colon tissue, down-regulate the protein expressions of cytosol PPARγ, tissue p-IKKβ, p-IκBα and nucleus NF-κBp65 in the colon tissue, decrease the p-IKKβ/IKKβ and p-IκBα/IκBα ratios, up-regulate the protein expressions of nucleus PPARγ, tissue SIRT1 and cytosol NF-κBp65 (<0.05 or <0.01, respectively), with a dose-effect relationship between the total triterpenoids of C. speciosa treated groups. These findings suggested that total triterpenoids of C. speciosa had a significantly therapeutic effect on UC mice induced by DSS, its mechanism might be related to the regulation of PPARγ/SIRT1/NF-κBp65 signaling pathway, the inhibition of pro-inflammatory factor formation and the up-regulation of protein expression of protective factors.
Animals ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Colon ; drug effects ; Dextran Sulfate ; Disease Models, Animal ; Intestinal Mucosa ; drug effects ; Mice ; Mice, Inbred C57BL ; PPAR gamma ; metabolism ; Random Allocation ; Rosaceae ; chemistry ; Signal Transduction ; drug effects ; Sirtuin 1 ; metabolism ; Transcription Factor RelA ; metabolism

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers ; Cohort Studies* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Lymph Nodes ; Nasopharynx ; Plasma ; Prognosis ; Radiotherapy* ; Tumor Burden*

OBJECTIVETo evaluate the sensitivity and specificity of CD8CD28/CD8CD28T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD).

METHODSForty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8CD28and CD8CD28T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8CD28/CD8CD28T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8T lymphocytes and the factors were analyzed.

RESULTSThe utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8CD28T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8CD28T cells, CD8CD28T cells, and especially CD8CD28/CD8CD28ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ=9.730, P=0.002; Χ=15.981, P=0.000). CD8CD28/CD8CD28ratio was significantly related to both BA (P=0.009) and surgery (P=0.038).

CONCLUSIONBoth decreased CD8CD28T cells and elevated CD8CD28T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.