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

ObjectiveTo investigate the effect of Shaoyaotang on diarrhea， inflammation， and intestinal flora in rats with dampness-heat diarrhea and explore the mechanism of therapeutic principle "treating incontinent syndrome with dredging method" of Shaoyaotang. MethodThe dampness-heat diarrhea model was induced by high temperature， high humidity， high sugar and fat diet， and pathogenic factors. The rats were divided into normal group， model group （normal saline）， Shaoyaotang group （5.62 g·kg^-1）， Rhei Radix et Rhizoma （RRER）-free Shaoyaotang group （5.15 g·kg^-1）， and RRER group （0.01 g·kg^-1）. The rats were treated correspondingly for five days， twice a day in the morning and evening. The diarrhea index was used to evaluate the antidiarrheal effect of each group three hours after the administration in the evening. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-2， and IL-6 in the serum were detected by enzyme-linked immunosorbent assay （ELISA） three hours after the last administration. The structure of intestinal flora in feces was characterized by 16sDNA. ResultCompared with the model group， the Shaoyaotang group， the RRER-free Shaoyaotang group， and the RRER group showed reduced diarrhea index （P<0.01）， with the onset rates ranking as the Shaoyaotang group>the RRER-free Shaoyaotang group>the RRER group. Those three groups with drug intervention all showed decreased levels of inflammatory factors （P<0.01）， especially the Shaoyaotang group， and no significant difference was observed between the RRER group and the RRER-free Shaoyaotang group. The abundance of pathogenic bacteria and conditioned pathogens （e.g. Escherichia-Shigella， Prevotella， Enterorhabdus， and Bacteroides） was reduced and the proliferation of probiotics （such as Ruminococcus， Turicibacter， and Lachnospiraceae） was increased in the groups with drug intervention （P<0.01）. For the structure of intestinal flora， the RRER group and the Shaoyaotang group were close to the normal group， and the RRER-free Shaoyaotang group was different from the other three groups （P<0.01）. ConclusionShaoyaotang can improve the outcome of rats with dampness-heat diarrhea through anti-inflammation and regulation of intestinal flora disorders. RRER in the prescription plays a key role in reducing the abundance of harmful bacteria and promoting the proliferation of probiotics， which is the key of Shaoyaotang in promoting the re-balance of intestinal flora. It also confirms the scientificity of treating dampness-heat diarrhea with RRER following the therapeutic principle "treating incontinent syndrome with dredging method".

OBJECTIVES: This study aims to investigate the incidence and severity of obstructive sleep apnea (OSA) in cleft patients with velopharyngeal insufficiency (VPI) after pharyngeal flap surgery (PFS) and explore the influence of operation age. METHODS: A retrospective study was conducted in 82 cleft patients after PFS. The patients were divided into two groups according to their age at the time of surgery. The incidence and severity of OSA were assessed at least 1.2 years (mean 6.0 years) postoperatively by polysomnography (PSG). RESULTS: The incidence rates of OSA were 20% in the adult group and 31% in the child group. No significant difference was found between the two groups ( CONCLUSIONS Some patients still have OSA average of 6.0 years after PFS, and operation ageis unrelated to the incidence and severity of OSA.
Adult ; Child ; Humans ; Pharynx ; Polysomnography ; Retrospective Studies ; Sleep Apnea, Obstructive/epidemiology* ; Velopharyngeal Insufficiency/etiology*

Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy; however, the underlying mechanism has not been fully elucidated. In this study, we aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules. Methods 8-week-old male db/db mice (n=8), a type 2 diabetic nephropathy model, administered with nuclear factor kappa-B (NF-κB) inhibitor parthenolide (PTN, 1 mg/kg) intraperitoneally every other day for 8 weeks, were as the treatment group. Meanwhile, the age-matched male db/m mice (n=5) and db/db mice (n=8) were treated with saline as the control group and type 2 diabetic nephropathy group. When the mice were sacrificed, blood and urine were collected to examine homeostasis model assessment of insulin resistance (HOMA-IR) and urine albumin creatinine ratio, and kidney samples were used to analyze histopathologic changes with periodic acid-Schiff (PAS) staining, NF-κB p65, phosphorylation of AKT (p-AKT), amnionless and cubilin expressions with immunohistochemistry as well as western blot, and the albumin uptake of renal tubules by using immunofluorescence. In addition, HKC cells were divided into the insulin group treated with insulin alone, the TNF-α group treated with insulin and tumor necrosis factor (TNF-α), and the TNF-α+PTN group exposed to PTN, insulin and TNF-α. The levels of albumin uptake and expression levels of NF-κB p65, p-IRS-1/IRS-1, p-AKT/AKT, amnionless and cubilin in HKC cells were measured. Results Compared with the db/db group, the db/db+PTN group demonstrated decreased levels of HOMA-IR (36.83±14.09 vs. 31.07±28.05) and urine albumin creatinine ratio (190.3±7.3 vs. 143.0±97.6 mg/mmol); however, the differences were not statistically significant (P>0.05). Periodic acid-Schiff staining showed PTN could alleviate the glomerular hypertrophy and reduce the matrix in mesangial areas of db/db mice. The renal expression of NF-κB p65 was increased and p-AKT (s473) decreased in the db/db group compared with the db/m group (P<0.05). PTN significantly reduced the renal expression of NF-κB p65 and ameliorated the decline of p-AKT (s473) compared with the db/db group (P<0.05). Compared with the db/m group, the expression of amnionless and cubilin decreased and albumin uptake in tubules were reduced in the db/db group (P<0.05), and PTN could significantly increase the expression of cubilin (P<0.05), and improve albumin uptake in tubules. Insulin promoted albumin uptake and the expression of amnionless and cubilin in HKC cells (P<0.05). TNF-α stimulated the expression of NF-κB p65, increased p-IRS-1 (s307) and reduced p-AKT (s473) in HKC cells (P<0.05). In the TNF-α+PTN group, the expression of NF-κB p65 declined and p-IRS-1 (s307) and p-AKT (s473) were restored, compared with the TNF-α group (P<0.05). The expression of amnionless and cubilin decreased in the TNF-α group (P<0.05), and PTN could significantly increase the expression of cubilin (P<0.05). Conclusions Inflammation caused damage to insulin signaling, which reduced amnionless-cubilin expression and albumin uptake. PTN could reduce inflammation and remodel the impaired insulin signaling pathway, which promoted the expression of cubilin and albumin uptake. Our study can shed light on the role of inflammation in the reduction of albumin uptake of renal tubules in type 2 diabetic nephropathy.
Albumins/pharmacokinetics* ; Albuminuria/urine* ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Cell Line ; Creatinine/urine* ; Diabetes Mellitus, Type 2/complications* ; Diabetic Nephropathies/metabolism* ; Humans ; Insulin Resistance ; Kidney Tubules, Proximal/metabolism* ; Male ; Mice ; NF-kappa B/metabolism* ; Receptors, Cell Surface/metabolism* ; Sesquiterpenes/pharmacology*

OBJECTIVE: To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05). CONCLUSION DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).

Objective: To study on the antitumor mechanism of artesunate in the treatment of liver cancer based on gas chromatography-mass spectrometry (GC-MS). Method: CellTiter-Glo^® Luminescent Cell Viability Assay was used to detect activity of artesunate with different concentrations (0, 12.5, 25, 50, 100 μmol·L^-1) on human liver cancer Huh7, SMMC-7721 cells for 24, 48, 72 h. GC-MS was employed to analyze the changes of metabolites of artesunate in two kinds of hepatoma cells (Huh7, SMMC-7721) for 24 h. The data was preprocessed by Postrun Analysis 4.41 workstation. Partial least squares-discriminant analysis (PLS-DA) was used to analyze two sets of differential metabolites and to analyze metabolic pathways of differential metabolites based on MetaboAnalyst 3.0 software. Result: Compared with the normal group, after two kinds of liver cancer cells was treated by artesunate, a total of 39 identical metabolites in the cells have undergone significant changes, which were mainly related to five metabolic pathways,including biosynthesis of aminoacyl-transfer RNA (tRNA), metabolism of alanine, aspartic acid and glutamic acid, metabolism of glycine, serine and threonine, metabolism of arginine and proline, metabolism of glutathione. Conclusion: Artesunate (12.5-100 μmol·L^-1) can inhibit the growth of liver cancer cells (Huh7, SMMC-7721), it mainly involves five metabolic pathways, which may be the pathway of artesunate against liver cancer.

Objective To explore the signal transduction mechanism of p38 mitogen activated protein kinase (p38MAPK) in human facial hypertrophic scar fibroblast (FB) differentiation into myofibroblasts(MFB).Methods Fibroblasts of primary culture were simple randomly assigned into two groups:cyclic stretch (control group) and cyclic stretch pre-treated with SB203580 (experimental group).Expression of P-p38MAPK and α-smooth muscle actin (α-SMA) protein were examined using Western blotting and expression of transforming growth factor β1 (TGF-β1) mRNA and α-SMA mRNA were examined using reverse transcription PCR(RT-PCR).Results In control group,the expressions of α-SMA,p38MAPK,TGF-β1 mRNA and α-SMA mRNA(0 h:0.134 ± 0.011,0.239 ± 0.015,0.214 ± 0.018,0.252 ± 0.010 ; 6 h:0.152±0.014,0.287 ±0.016,0.288 ±0.011,0.277 ±0.013; 12 h:0.172 ±0.017,0.320 ±0.017,0.335 ±0.013,0.297 ± 0.006),were significantly increased with loading time (6 h ＞ 0 h; 12 h ＞ 0 and 6 h).In experimental group (pre-treated with SB203580),the expressions of α-SMA,p38MAPK,TGF-β1 mRNA,α-SMA mRNA(6 h:0.116 ±0.017,0.128 ±0.016,0.134 ±0.014,0.163 ±0.009; 12 h:0.149 ± 0.013,0.136 ±0.018,0.144 ±0.013,0.187 ±0.010) on corresponding time decreased sharply compared with those in control groups (6,12 h).Conclusions The human facial hypertrophic scar fibroblasts differentiation in response to cyclic stretch was mediated by p38MAPK phosporylation.

BACKGROUNDCardiac resynchronization therapy (CRT) with biventricular pacing improves cardiac function, functional capacity and quality of life in selected patients with heart failure. The current study aimed to evaluate the efficacy of the intracardiac electrogram (IEGM)-based optimization method, QuickOpt(TM), in Chinese patients treated with CRT.

METHODSAortic time velocity integrals (AVTI) achieved at the sensed atrioventricular (AV), paced AV and interventricular (VV) interval settings recommended by both QuickOpt(TM) and standard echocardiographic optimization were measured in 101 patients. Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient (ICC).

RESULTSThe ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV (ICC = 0.9683 (0.9535 - 0.9785)), paced AV (ICC = 0.9642 (0.9475 - 0.9757)) and VV (ICC = 0.9730 (0.9602 - 0.9817)) interval settings determined by the two optimization methods. The average time required by echocardiographic optimization and by QuickOpt(TM) were (78.32 ± 32.40) minutes and (1.98 ± 1.64) minutes respectively (P < 0.0001).

CONCLUSIONThe QuickOpt(TM) algorithm provides a quicker, simpler and reliable alternative to the standard method for timing cycle optimization.

Adult ; Aged ; Aged, 80 and over ; Cardiac Resynchronization Therapy ; methods ; Electrophysiologic Techniques, Cardiac ; methods ; Female ; Heart Failure ; therapy ; Humans ; Male ; Middle Aged ; Prospective Studies

This study was aimed to investigate the immunological effect of modified dendritic cells (DC) which inducing cytotoxic T cells (CTL) against lymphoma cells. The DC were isolated from the lymph node and peripheral blood of patients with diffuse large B cell lymphoma (DLBCL). DC were transfected with recombinant adenovirus vector carrying human p53 gene (rAd-p53-DC). The expression of p53 gene was detected by flow cytometry. Western-blot was used to detect the expression of P53. ELISA was used to detect IL-12 level in supernatant. The mixed lymphocyte reaction (MLR) was used to detect the proliferative ability of auto-lymphocyte stimulated by DC. The lactate dehydrogenase (LDH) release test was used to determine the cytotoxicity of CTL. The results indicates that the expressions of DC surface molecule (except for CD1a) such as CD83, CD80, CD86 and HLA-DR were significantly higher in experiment group than that in control group and blank control group. The secretion of IL-12 in supernatant was higher in experiment group than that in control group. The autologous T lymphocyte proliferation and cytotoxic activity against the same kind of DLBL-cells increased in experiment group as compared with control group and blank control group (P < 0.05). The ability to stimulate T lymphocyte proliferation increased with the rising of the ratio of DC and T lymphocyte. However, there was statistically significant difference between rAd-p53-DC derived from Lymph node and peripheral blood (P < 0.05). It is concluded that rAd-p53-transfected DC can induce CTL response in vitro against lymphoma cells.
Adenoviridae ; Cell Line, Tumor ; Dendritic Cells ; cytology ; immunology ; Genes, p53 ; Genetic Vectors ; Humans ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Lymphoma, Large B-Cell, Diffuse ; blood ; immunology ; Transfection

BACKGROUNDPrevious studies have proved the renal protective effects of anisodamine in patients with septic shock. The aim of this study was to investigate anisodamine for the prevention of contrast induced nephropathy (CIN) in patients with acute coronary syndrome (ACS).

METHODSConsecutive ACS patients undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to one of two groups: patients in the anisodamine group (ANI group) were assigned to receive intravenous infusions of anisodamine by an adjusted-dose (0.1 - 0.2 µg × kg(-1)× min(-1)) from the PCI procedure to 24 hours after PCI, and the control group (CON group) received 0.9% isotonic saline of the same volume. All patients were hydrated for 6 to 12 hours before and 12 hours after PCI. Blood samples were taken on the day of PCI and at 24, 48 and 72 hours after PCI to measure the serum creatinine (SCr).

RESULTSA total of 177 patients were involved in the study, 88 in the ANI group and 89 in the CON group. In both groups, the SCr concentrations significantly increased after PCI, with the peak value occurring at 48 hours. At 72 hours, the SCr concentration in the ANI group retuned to the baseline level (P > 0.05), but the SCr concentration in CON group was still higher than baseline level (P < 0.01). The SCr concentrations at 48 and 72 hours after PCI were much lower in the ANI group than those in the CON group (both P < 0.01). The estimated glomerular filtration rate (eGFR) significantly decreased after PCI, the lowest value occurred at 48 hours. In the ANI group, the eGFR at 72 hours was similar to the baseline level. In the CON group, the eGFR failed to return to baseline at 72 hours (P < 0.01). The eGFR at 24, 48 and 72 hours after PCI were higher in the ANI group (all P < 0.05). The incidence of CIN in the ANI group was lower than that in the CON group within 72 hours after PCI (P < 0.05). The results of multiple Logistic regression proved that both diabetes and left ventricular ejection fraction (LVEF) were independent predictors of CIN, and treatment with anisodamine was an independent preventive factor of CIN (OR 0.369 and 95%CI 0.171 to 0.794, P = 0.011). No serious side effects were found in the ANI group.

CONCLUSIONIntravenous infusion of anisodamine during and after elective PCI may safely prevent the occurrence of CIN in ACS patients.

Acute Coronary Syndrome ; therapy ; Adult ; Aged ; Angioplasty, Balloon, Coronary ; Contrast Media ; adverse effects ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; chemically induced ; epidemiology ; prevention & control ; Logistic Models ; Male ; Middle Aged ; Solanaceous Alkaloids ; adverse effects ; therapeutic use