OBJECTIVETo explore the effect of homoharringtonine(HHT) combined with imatinib(IM) on proliferation and apoptosis of K562/G01 cells and its potential mechanism.

METHODSK562/G01 cells were cultured with HHT and/or IM. CCK-8 assay was used to detect cell proliferation. Cell apoptosis and phosphorylated tyrosine levels were analyzed by flow cytometry. The expression levels of p210, PI3K, p-Akt and Akt protein were determined by Western blot.

RESULTSCompared with HHT or IM alone, drug combination significantly inhibited cell proliferation and induced apoptosis of K562/G01 cells (both P< 0.05). HHT combined with IM could inhibit the levels of phosphorylated tyrosine and phosphorylated Crkl and downregulate the expressions of p210, PI3K and p-Akt in K562/G01 cells.

CONCLUSIONHHT combined with IM can synergistically inhibit proliferation and induce apoptosis of K562/G01 cells by suppressing the p210 expression and its kinase activity.

Themedical's () infantgenre in western Hunan Province is one of the most famous infantgenres in China. Based on physiological and pathological characteristics of infants, generation-inhibition theory of five-elements andmedical's promotion-inhibition theory of five-meridians, theprotocol of "" was flexibly adjusted; according to different constitution types, including lung-deficiency type, spleen-deficiency type, kidney-deficiency type,-deficiency type,-deficiency type,-deficiency type, phlegm-wet type, phlegm-heat type, different protocols were adopted to prevent or reduce the asthma recurrence and reach the aim of regulating constitution and disease prevention.

OBJECTIVETo investigate the effects of AMPK agonist Acadesine (AICAR) on growth inhibition of K562 cells and their sensitivity to imatinib (IM).

METHODSK562 cells were cultured with different concentrations of AICAR alone or its combination with IM for 48 hours, the CCK-8 assay was used to detect cell proliferation, the cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression levels of Cyclin D1, Cyclin E1 and Caspase 3 protein were determined by Western blot.

RESULTSAICAR inhibited the proliferation of K562 cells in dose-dependent manner, and their IC50 value was 0.45 mmol/L at 48 hours. AICAR could induce arrest of K562 cells in G1 phase and down-regulated the protein expression levels of Cyclin D1 and Cyclin E1; whereas it didn't influence the cell apoptosis. Additionally, the growth inhibition of cells induced by IM was enhanced by AICAR.

CONCLUSIONAICAR can inhibit the proliferation of K562 cells by arresting the cell cycle and enhancing the sensitivity of K562 cells to IM.

Aminoimidazole Carboxamide ; analogs & derivatives ; pharmacology ; Apoptosis ; Caspase 3 ; metabolism ; Cell Cycle Checkpoints ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Humans ; Imatinib Mesylate ; pharmacology ; K562 Cells ; drug effects ; Oncogene Proteins ; metabolism ; Ribonucleosides ; pharmacology

OBJECTIVETo observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.

METHODSTotally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared.

RESULTSDifferent treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both).

CONCLUSIONSBoth constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.

Antiviral Agents ; therapeutic use ; Gene Frequency ; HLA-DQ alpha-Chains ; genetics ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Medicine, Chinese Traditional ; Polyethylene Glycols ; therapeutic use ; Polymorphism, Genetic ; Recombinant Proteins ; therapeutic use ; Remission Induction ; Yin Deficiency ; genetics

Humans ; Laryngeal Diseases ; surgery ; Larynx ; surgery ; Microsurgery ; instrumentation ; Otorhinolaryngologic Surgical Procedures ; instrumentation ; Surgical Instruments

PURPOSE: The universal organic solvent dimethyl sulfoxide (DMSO) can be used as a differentiation inducer of many cancer cells and has been widely used as a solvent in laboratories. However, its effects on breast cancer cells are not well understood. The aim of this study is to investigate the effect and associated mechanisms of DMSO on mouse breast cancer. METHODS: We applied DMSO to observe the effect on tumors in a mouse breast cancer model. Tumor-associated macrophages (TAMs) were tested by flow cytometry. Ex vivo tumor microenvironment was imitated by 4T1 cultured cell conditioned medium. Enzyme-linked immunosorbent assays were performed to detect interleukin (IL)-10 and IL-12 expression in medium. To investigate the cytotoxicity of DMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed. RESULTS: We found that DMSO produced tumor retardation when injected into mouse peritoneal cavities in a certain concentration range (0.5-1.0 mg/g). Furthermore, as detected by flow cytometry, TAM subtypes were found to be transformed. We further imitated a tumor microenvironment in vitro by using 4T1 cultured cell conditioned medium. Similarly, by using low concentration DMSO (1.0%-2.0% v/v), TAMs were induced to polarize to the classically activated macrophage (M1-type) and inhibited from polarizing into the alternatively activated macrophage (M2-type) in the conditioned medium. IL-10 expression in tumors was reduced, while IL-12 was increased compared with the control. Furthermore, we reported that 2.0% (v/v) DMSO could lead to cytotoxicity in peritoneal macrophages after 48 hours in MTT assays. CONCLUSION: Our findings suggest that DMSO could exert antitumor effects in 4T1 cancer-bearing mice by reversing TAM orientation and polarization from M2- to M1-type TAMs. These data may provide novel insight into studying breast cancer immunotherapy.
Animals ; Breast Neoplasms* ; Breast* ; Cells, Cultured ; Culture Media, Conditioned ; Dimethyl Sulfoxide* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunotherapy ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Macrophages* ; Macrophages, Peritoneal ; Mice* ; Tumor Microenvironment

This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ≥ 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ≥ 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Biomarkers, Tumor ; metabolism ; Child ; Epstein-Barr Virus Infections ; Female ; Hodgkin Disease ; diagnosis ; virology ; Humans ; Male ; Middle Aged ; Prognosis ; Viral Matrix Proteins ; metabolism ; Young Adult

OBJECTIVETo compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN).

METHODSOne hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit.

RESULTSThe total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment.

CONCLUSIONThe fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Neuralgia, Postherpetic ; therapy ; Pain Measurement ; Treatment Outcome

OBJECTIVETo evaluate the feasibility of the Shikani Optical Stylet (SOS)-guided intubation through a new Intubating Laryngeal Airway (ILA) in anticipated difficult airways caused by scar contracture of the face and neck.

METHODSThirty-three adult patients with anticipated difficult airways undergoing selective faciocervical scar plastic surgery under general anesthesia were enrolled in this study. After anesthesia induction, a size 2.5, 3.5 or 4.5 ILA was inserted. Following good lung ventilation being verified, the SOS preloaded with an endotracheal tube was inserted via the ILA. Once the clear vocal cords came into view under the SOS, the endotracheal tube was advanced through glottis into the trachea.

RESULTSThe ILA provided an effective airway in all patients. Intubation was successful at the first attempt on 22/33(66.7%) occasions and at the second attempt on 6/33 (18.2%). Intubation failed in 5 (15.1%) patients who suffered from severe limitation of head extension due to scar contracture of the neck. These patients' tracheas were finally intubated using a fibreoptic bronchoscope via the ILA.

CONCLUSIONSThe SOS-guided intubating method via the ILA is a feasible technique in patients with scar contracture of the face and neck. However, in patients with severe limitation of head extension, the use of SOS cannot be recommended. The SOS can be used as an alternative apparatus when the fibreoptic bronchoscope is not available.

Adolescent ; Adult ; Cicatrix ; complications ; Contracture ; complications ; Face ; Humans ; Intubation, Intratracheal ; instrumentation ; methods ; Middle Aged ; Neck

OBJECTIVETo compare the clinical effectiveness of blind intubation through the Cookgas intubating laryngeal airway(CILA) or Fastrach intubating laryngeal mask airway(FT-LMA) for anticipated difficult tracheal intubation.

METHODSEighty-six patients with anticipated difficult tracheal intubation who were undergoing elective plastic surgery under general anesthesia were randomly allocated into CILA group(n=43) and FT-LMA group(n=43) . After general anesthesia being induced and CILA or FT-LMA being inserted, the patients were treated with blind intubation through CILA or FT-LMA. In each case, the number and the time of intubating laryngeal airway(ILA) insertion and blind intubation attempts and ILA removal were recorded. The view of glottis under fiberoptic bronchoscope(FOB) via CILA or FT-LMA was recorded. In addition, noninvasive blood pressure and heart rate were recorded before and after intravenous anesthetic induction, at ILA insertion, at intubation, at ILA removal and every minute thereafter for 5 minutes.

RESULTSCILA or FT-LMA was inserted successfully in all 86 patients. The rate of the first successful insertion was not significantly different between two groups(P>0.05) . In CILA group, the first intubation attempt succeeded in 35 patients;5 and 2 cases were intubated blindly at the second and the third attempt, one patient failed who was intubated successfully by FOB via CILA. In FT-LMA group, 32 patients were intubated successfully at the first attempt, 4 at the second attempt, 3 at the third attempt, and 4 cases failed, three of them were intubated smoothly with FOB through FT-LMA, one failed patient was intubated by FOB. The time of FT-LMA insertion(34.2∓13.9) s was significantly longer when compared with CILA(22.4∓18.9) s (P<0.05) . However, the time of blind intubation through CILA and FT-LMA [(46.0∓26.7) s vs.(51.8∓41.1) s]and the time of ILA removal[(39.3∓11.9) s vs.(35.3∓10.4) s] were not significantly different between groups(P>0.05) . Hemodynamic changes during blind intubation in the two groups showed no significant differences(P>0.05) .

CONCLUSIONSBlind intubation via CILA or FT-LMA is safe and effective for anticipated difficult tracheal intubation. Nevertheless, CILA is easier to be inserted, with relatively higher success rate of blind intubation.

Adolescent ; Adult ; Anesthesia, General ; Bronchoscopy ; Humans ; Intubation, Intratracheal ; instrumentation ; Laryngeal Masks ; Middle Aged ; Young Adult