Objective To investigate the instant clinical efficacy of intra-arterial infusion of fasudil combined with routine anti-vasospasm for symptomatic cerebral vasospasm (SCVS). Methods The clinical data of 21 patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysm, who were admitted to authors' hospital during the period from May 2010 and February 2014, were retrospectively analyzed. The lesions included Fisher gradeⅡ(n=2), gradeⅢ (n=16) and gradeⅣ (n=3). Endovascular embolization of the aneurysm was carried out within 48 hours after the confirmation of the diagnosis with total cerebral DSA;no bleeding occurred during the operation and routine anti-vasospasm therapy was given. Within 4-9 days after the onset of the disease, all 21 patients presented SCVS. Half dose systemic heparinization, superselective intra-arterial infusion of fasudil (30 mg fasudil+250 ml saline, lasting for 30 min) were adopted. Reexamination of angiography performed at 15 min after fasudil infusion was employed, and the results were evaluated with NIHSS score by comparing the preoperative findings. Results Imaging examination performed after the treatment showed that significant improvement was obtained in 15 patients and no obvious changes in 6 patients. Clinical symptoms were remarkably improved in 11 patients, partially improved in 4 patients and remained unchanged in 6 patients. The mean NIHSS score was improved from preoperative 28.6 to postoperative 21.2. Conclusion For the treatment of symptomatic cerebral vasospasm, superselective intra-arterial infusion of fasudil is effective and safe, and it has good clinical application value.

OBJECTIVETo explore the efficacy and feasibility of dog days moxibustion plaster therapy in treatment of allergic rhinitis of different patterns/syndromes.

METHODSAllergic rhinitis of lung deficiency and invasion of cold, spleen qi deficiency and kidney yang deficiency, 56 patients for each pattern/syndrome were randomized into a plaster therapy group and a nasal spray group, 28 cases in each one. In the plaster therapy group, according to the pattern/syndrome differentiation, with literature retrieval method, 3 acupoints of high frequency utility in clinic were selected as one group in acupoint plaster therapy. For lung deficiency and invasion of cold pattern/syndrome, Feishu (BL 13), Fengmen (BL 12) and Hegu (LI 4) were selected. For spleen qi deficiency pattern/syndrome, Pishu (BL 21), Zusanli (ST 36) and Dazhui (GV 14) were selected. For kidney yang deficiency pattern/ syndrome, Shenshu (BL 23), Dingchuan (EX-B 1) and Bailao (EX-HN 15) were selected. Separately, on July 13, 2013, July 23, 2013, August 2, 2013 and August 12, 2013, the aucpoint plaster therapy was applied, 2 to 4 h (1 to 2 h for children) each time. In the nasal spray group, beclometasone dipropionate aqueous nasal spray, 2 presses one nostril each time, 2 to 3 times a day, continuously for 4 weeks. The symptom score and efficacy were compared before and after treatment in the patients of the two groups.

RESULTSThe symptom scores of 3 patterns/syndromes were all apparently improved after treatment as compared with those before treatment in the patients of the two groups (all P<0.05), and the result in the plaster therapy group was better than that of the nasal spray group (P<0.05, P<0.01). For lung deficiency and invasion of cold pattern/syndrome, the total effective rate was 87.3% (20/24) in the plaster therapy group, better than 84.6% (22/26) in the nasal spray group (P<0.05). For spleen qi deficiency pattern/syndrome, the total effective rate was 83.3% (20/24) in the plaster therapy group, obviously better than 76.9% (22/26) in the nasal spray group (P<0.05). For kidney yang deficiency pattern/syndrome, the total effective rate was 79.2% (19/24) in the plaster therapy group, better than 76.9% (22/26) in the nasal spray group (P<0.05).

CONCLUSIONThe dog days moxibustion plaster therapy achieves definite efficacy on allergic rhinitis at the acupoints selected based on the differentiation of different patterns/syndromes and the efficacy is better than beclometasone dipropionate aqueous nasal spray.

Acupuncture Points ; Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Child ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Rhinitis, Allergic ; drug therapy ; therapy ; Yang Deficiency ; drug therapy ; Young Adult

OBJECTIVETo explore the effects of arecoline on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism.

METHODSForty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model. rats were randomly divided into 5 groups (n = 8): control group, model group and model group were treated with different dose (0, 0.5, 1, 5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot.

RESULTS1.5 mg/kg arecoline could significantly decrease the level of fasting blood glucose, blood lipid, blood insulin level and liver G6Pase, PEPCK, IL-6, TNF-alpha mRNA level in type 2 diabetes rats. 1.5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression.

CONCLUSIONArecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the creased glucose metabolism and inflammation related genes expression.

Animals ; Arecoline ; pharmacology ; Diabetes Mellitus, Experimental ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Glucose Transporter Type 4 ; metabolism ; Glucose-6-Phosphatase ; metabolism ; Insulin Resistance ; Interleukin-6 ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Phosphoenolpyruvate Carboxykinase (GTP) ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Receptors, Steroid ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

OBJECTIVETo study the variation of the hemorheology in patients with chronic hepatitis B and study its relations with HBV DNA, liver function and oxidative stress markers.

METHODSIndices for hemorheology, oxidative stress markers, liver function, and HBV DNA were measured in 55 patients with chronic hepatitis B and correlative analysis was made.

RESULTSThe low-shear whole blood viscosity (BV), RBC aggregation index were significantly higher in hepatitis B group than those in the control group (P < 0.05), Hematocrit (HCT), the low-shear BV, RBC aggregation index were significantly higher in the patients whose ALT was higher than the patients whose ALT was normal and the controls. No significant difference was found in HBV DNA and indices of hemorheology (P > 0.05), nor in indices of hemorheology and oxidative stress markers (P > 0.05).

CONCLUSIONThere is disturbance of microcirculation and oxidative stress in the body of patients with chronic hepatitis B. The hemorheology and oxidative stress markers should be regarded as useful indexes in patients with chronic hepatitis B in addition to HBV markers.

Adolescent ; Adult ; Alanine Transaminase ; blood ; Blood Viscosity ; Child ; DNA, Viral ; blood ; genetics ; Female ; Hematocrit ; Hepatitis B virus ; genetics ; physiology ; Hepatitis B, Chronic ; blood ; virology ; Host-Pathogen Interactions ; Humans ; Male ; Malondialdehyde ; blood ; Middle Aged ; Vitamin E ; blood ; Young Adult

OBJECTIVETo investigate nitric oxide (NO) and nitric oxide synthase (NOS) in patients with chronic hepatitis B.

METHODSNitric oxide and nitric oxide synthase, including inducible NOS (iNOS) and constitutive NOS (cNOS), were measured in patients and control groups, then were statistically analyzed.

RESULTSNO and iNOS were significantly higher in patients with hepatitis B than in the controls (P < 0.05). NO and iNOS were significantly higher in patients with increased ALT than in the controls and in patients with normal ALT (P < 0.05). NO was significantly higher in patients with normal ALT than in the controls (P < 0.05). cNOS were not significant different among these groups. NO and iNOS significantly correlated with ALT in patients with hepatitis B (r=0.367 and r=0.474). No significant relationship was found among NO, NOS and HBV DNA. Among different genotype groups, NO and NOS had no significant difference.

CONCLUSIONNO and NOS were higher in patents with chronic hepatitis B. In patients with increased ALT, NO's damage was severe. In patients with normal ALT, there was no significant damage caused by NO. NO should be detected in patients with hepatitis B in addition to HBV markers.

Adolescent ; Adult ; Alanine Transaminase ; blood ; DNA, Viral ; genetics ; Female ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; metabolism ; virology ; Humans ; Male ; Middle Aged ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Young Adult

OBJECTIVETo explore the roles of intracellular cholesterol metabolism in neuroendocrine (NE) differentiation of prostate cancer based on an androgen-independent prostate cancer NE cell model induced by androgen deprivation.

METHODSLNCaP cells were cultured in androgen-depleted medium, and NE phenotypes were identified by observing the changes in cell morphology, molecular markers (SgIII, NSE and CgA) and cell proliferation. The expression and distribution of cholesterol and Sg III were determined by immunofluorescence staining. The expressions of the key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake were detected by semi-quantitative RT-PCR.

RESULTSThe LNCaP cells showed shrinking bodies and extending axons after androgen deprivation, and all the molecular markers, such as Sg III, NSE and CgA, significantly increased in a time-dependent manner, while the cell proliferation was obviously inhibited (P < 0.05). The cholesterol distribution in the LNCaP cells after NE differentiation presented remarkable aggregation at the axon terminals. However, there were no significant differences in the expression of cholesterol between the two types of cells, nor in the changes of the expressions of key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake (P > 0.05).

CONCLUSIONTransient androgen depletion could successfully induce NE differentiation of LNCaP cells, and the intracellular cholesterol could re-distribute into axon terminals to enhance the formation of neurosecretory granules.

Androgens ; pharmacology ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Cholesterol ; metabolism ; Humans ; Male ; Neurosecretory Systems ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, LDL ; metabolism ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism

BACKGROUNDLinear ablation of left atrium (LA) guided by three dimensional (3-D) electroanatomical mapping (Carto) has been used in many centres worldwide for the treatment of atrial fibrillation (AF) instead of pure anatomical approaches. There were little data about linear ablation of LA guided by Carto and double Lasso catheters in China. We report the results of linear ablation of LA guided by both Carto and double Lasso catheters.

METHODSAfter the anatomical model of LA and all pulmonary veins (PVs) had been established, circumferential ablations of the left pulmonary vein antrum and the right pulmonary vein antrum were performed with 2 circumferential mapping catheters (Lasso) placed within the ipsilateral superior and inferior PVs. The endpoint of ablation was abolishment or dissociation of the pulmonary vein potentials (PVPs). Oral amiodarone or propafenone was taken for at least 3 months by patients with persistent AF, permanent AF or those whose PVPs had not been isolated completely. The recurrence of atrial tachyarrhythmias was observed 3 months after the procedure.

RESULTSThere were 106 patients (mean age, 51.4 +/- 9.9 years). Seventy-eight patients had paroxysmal AF, 12 persistent AF and 16 permanent AF. Onset of atrial fibrillation occurred in 52 patients during ablation procedure. Thirty-two patients restored to sinus rhythm eventually after the procedure. Abolishment or dissociation of PVPs was accomplished during the procedure in 94 patients (88.7%). The duration of procedure and exposure to X-ray were (213 +/- 45) minutes and (32.5 +/- 12.8) minutes, respectively. Among the 87 patients followed up for over 3 months, 62 were free of atrial tachyarrhythmias (including 8 patients who were still taking oral amiodarone). The success rate was 71.3% in the first procedure. Two patients had pericardial effusion treated by pericardial puncture and effusion drainage. No pulmonary vein stenosis, atrioesophageal fistula, stroke or procedural death occurred.

CONCLUSIONSCombination of double Lasso catheters with 3-D electroanatomical mapping to guide the linear ablation of left atrium procedure can confirm the isolation of PVPs.

Adult ; Aged ; Atrial Fibrillation ; physiopathology ; surgery ; Catheter Ablation ; methods ; Electrophysiologic Techniques, Cardiac ; methods ; Female ; Heart Atria ; surgery ; Humans ; Male ; Middle Aged ; Pulmonary Veins ; physiopathology

BACKGROUNDInterleukin-13 (IL-13) is recognized to be a key modulator in the pathogenesis of Th2-induced allergic inflammation. Transcription factors GATA3 and NFAT1 have been both implicated in the regulation of Th2 cytokines. We previously demonstrated the GATA3-NFAT1 association during human T cell activation. However, the function of the GATA3-NFAT1 complex in Th2 cytokines regulation is still unknown. Small interference RNA (siRNA) was constructed to knock down GATA3 expression in Hut-78 cells to investigate the possible role of GATA3-NFAT1 complex in IL-13 transcription.

METHODSCells were stimulated with anti-CD3 plus anti-CD28 antibodies to mimic in vivo antigen-mediated co-stimulation; the expression of IL-13 mRNA was determined by real-time PCR; chromation immunoprecipitation (CHIP) assay was employed to investigate the NFAT1 binding to IL-13 promoter.

RESULTSGATA3 siRNA suppressed the expression of GATA3 both in mRNA and protein levels in Hut-78 cells. The binding of NFAT1 to IL-13 promoter was inhibited by GATA3 siRNA in activated T cells, which was followed by the reduction of IL-13 transcription.

CONCLUSIONGATA3-NFAT1 complex may play an important role in the regulation of IL-13 transcription in human T cells.

Cells, Cultured ; GATA3 Transcription Factor ; antagonists & inhibitors ; genetics ; Humans ; Interleukin-13 ; genetics ; NFATC Transcription Factors ; metabolism ; Promoter Regions, Genetic ; RNA, Small Interfering ; genetics ; T-Lymphocytes ; metabolism ; Transfection