Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the role and mechanism of sine oculis homeobox 1(Six1),a nephrogenic transcription factor,in regulating injury repair after acute kidney injury(AKI).Methods C57BL/6J mice were inflicted with renal ischemia reperfusion(IR)injury to establish AKI model,and then the serum samples and kidney tissues were collected at days 1,2,and 3 after modeling.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels were measured and renal morphology was observed with HE staining.The expression and distribution of nephrogenic molecules(Six1 and Pax2,etc.)and cell proliferation/migration genes(Cyclin A1,MMP9,etc.)were detected with RT-PCR,Western blotting,and immunofluorescence assay and immunohistochemical assay.The expression of apoptosis pathway(Bc12,Caspase3,etc.)and cell proliferation related molecules were evaluated in Six1 overexpression/knockout human epithelial cells(HK2)with CoCl2-induced injury.Additionally,after the adeno-associated viruses carrying Six1 overexpression vector were used to overexpress the molecule in the mice,the expression of Six1 and other related molecules were detected after IR injury modeling.Results After renal IR injury,Six1 was significantly activated in epithelial cells,the expression of nephrogenic and cell proliferation/migration molecules(Pax2,Cyclin A1,MMP9,etc.)was obviously up-regulated(P＜0.05),which was positively correlated with Six1 expression,while the proliferation/migration molecules(Ki67,MMP9)were also localized within the tubular epithelial cells.In cellular models of Six1 overexpression,the expression levels of nephrogenic and cell proliferation/migration molecules(Pax2,Cyclin A1,MMP9,etc.)were also notably up-regulated(P＜0.05).In the mice with renal overexpression of Six1,the nephrogenic molecules as well as anti-apoptotic ones(Six2,Pax2,Bc12,etc.)were up-regulated,while the expression of kidney injury-related molecule(Kim1)in kidneys was reduced in the renal tissues.While,in 2 d after IR injury,the anti-apoptotic gene(Bc12,Stat3)was significantly up-regulated(P＜0.05),and the apoptotic and injury molecules(Kim1,Caspase3)showed remarkable down-regulation(P＜0.05)in the mice with renal Six1 overexpression.Furthermore,CoCl2-inducion significantly decreased the cell proliferation rate in the Six1 knockoutgroup(TCMK1-Six1-/-)(P＜0.05)but increased the rate in the Six1 overexpression group(TCMK1-Six1)when compared to the control cells(P＜0.05).And,the expression of nephrogenic,anti-apoptotic pathways and cell proliferation/migration molecules(Pax2,Bc12,Cyclin A1,MMP9,etc.)were reduced in TCMK1-Six1-/-group,and apoptosis and kidney injury molecules(Caspase3,Kim1)were significantly down-regulated in TCMK1-Six1 group(P＜0.05).Conclusion Activation of Six1 after AKI can promote the proliferation/migration of renal tubular epithelial cells by up-regulating nephrogenic molecules and inducing anti-apoptotic pathway molecules,and then,participate in IR-induced renal injury repair.

The Qa-1 in mice is homologous to human leukocyte antigen E(HLA-E), and both of them belong to the non-classical major histocompatibility complex I b(MHC-I b) molecules. Qa-1 is capable of presenting self or exogenous antigen peptides to interact with two distinct receptors, namely T cell receptor (TCR) and natural killer cell group 2 member A (or C) (NKG2A/C), thus playing an important role in immune response and regulation. Qa-1-restricted regulatory CD8⁺ T cell (CD8⁺ Treg) is one of the most studied CD8⁺ Treg subgroups, which can maintain immune homeostasis and autoimmune tolerance by exerting immunosuppressive effects. Consequently, Qa-1-restricted CD8⁺Treg cells are closely associated with the occurrence and development of various clinical diseases, such as tumors, infections, autoimmune diseases, and transplant rejections. This paper provides a comprehensive review of the phenotypic characteristics, functional effects, regulatory mechanisms of Qa-1-restricted CD8⁺ Treg cells, as well as the latest research progresses of Qa-1-restricted CD8⁺ Treg cells involved in the pathogenesis of infectious diseases.
Humans ; Animals ; T-Lymphocytes, Regulatory/immunology* ; Histocompatibility Antigens Class I/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Communicable Diseases/immunology*

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
Animals ; Inflammation ; Mice ; NF-kappa B/metabolism* ; Particulate Matter/toxicity* ; Signal Transduction ; Sirtuin 2/metabolism* ; Transcription Factor RelA/metabolism*

OBJECTIVE:To investigate the characteristics and regularity of ADR induced by Iobitridol injection,and to provide reference for clinical drug use.METHODS:In retrospective study,the information of 72 patients suffering from ADR induced by Iobitridol injection were collected from our hospital during Jul.2015 to Jul.2016,and then statistical analysis was conducted in respects of age,gender,primary disease,organs/system involved in ADR,clinical manifestations,relationship evaluation and degree,occurrence time,outcomes,etc.RESULTS:Among 72 cases of ADR,the number of female was about twice of that in male.The age mainly distributed in the range of 50 to 80 years old (80.56％).ADR mainly occurred in skin and its appendants (30.57％),followed by systemic reactions (22.93％) and circulatory system (21.66％).ADR occurred within 20 min after medication (38.89％).58.33％ of ADR patients were cured,and 41.67％ were recovered.CONCLUSIONS:During the application of Io bitridol injection,a detailed understanding should be obtained about the patient's condition,medical history and the results of the examinations.Medical staff should inform the patient of the possible allergic symptoms,and do a good emergency preparation.

OBJECTIVE:To investigate the curative effect and economics of prostaglandins drugs in the treatment of glauco-ma,and to provide reference for clinical medication. METHODS:In retrospective study,a total of 790 glaucoma patients were di-vided into latanoprost group(62 cases),travoprost group(356 cases)and bimatoprost group(372 cases)according to therapy regi-men. They were given relevant medicine. Total effective rate of 3 groups were calculated,and the cost-minimization method was used for pharmacoeconomics evaluation. RESULTS:The total effective rate of 3 groups were 87.10%,84.27%,76.08% respective-ly,without statistical significance(P>0.05). The cost of them were 208.00 yuan,225.00 yuan and 173.00 yuan,and that of bima-toprost group was the lowest. The results of sensitivity analysis was in line with that of cost-minimization analysis. CONCLU-SIONS:For glaucoma,bimatoprost is more economical than latanoprost and travoprost.

At present the study of Marine antineoplastic drugs has already become the focus of concern around the world, Marine natural products has become an important source of clinical anti-cancer drugs. Ecteinascidin-743 from the Caribbean sea squirts Ecteinascidia turbinata extraction have been the ocean alkaloid, antitumor activity is significantly higher than the current widely used clinical antitumor drugs, inhibit a wide variety of tumor cell activity such as leukemia, ovarian cancer, soft tissue sarcoma, melanoma, cervical cancer, breast cancer, colorectal cancer, kidney cancer, prostate cancer, lung cancer and non-small cell lung cancer and other tumor cells, is the first successful application to the oceans, clinical antitumor drugs. In this paper, the drug synthesis, pharmacological and clinical research progress were reviewed.

Objective To study the quality control of yinpian of Isatis Root.Methods Optical microscope was used to identify the microscopic features,TLC was adopted to identify the arginine in Isatis Root,and HPIC-ELSD was used to detect the quality of arginine.Results and Conclusion There is no difference between yinpian and crude powder of Isatis Root.Arginine can be detected bv TLC.The moisture contents.the total ash contents and the acid-insoluble ash contents in the yinpian should be less than 9.0%,10.0%,and 2.0% respectively;while the alcohol-soluble extractive contents and the contents of arginine in Isatis Root should be more than 25.0% and 2.01% respectively.

OBJECTIVE:To design intermittent intravenous drip dose regimen of antibiotics. METHODS: The pharmacokinetic data were computed using the multidoses function method taking cefazolin,ceftriaxone and amikacin as examples. Then computation program was programmed using Excel software based on pharmacokinetic parameters combined with pharmacodynamic parameters to design rational dosage regimen. RESULTS: The bactericidal effect of time-dependent antibiotics was chiefly dependent on the time during which the drug blood concentration was higher than minimal inhibitory concentration(MIC).For those antibacterials with short elimination half life(t1/2)in plasma,the best regimen was to give patients the med-icine in a small average divided dose or continuous medication. For those with(t1/2) greater than 12～24 h,single dose admin-istration was advisable. For concentration-dependent antibiotics,the best PK/PD parameters for optimal clinical antibiotic effect were Cmax/ MIC,and which should be administered in single time (daily dose). CONCLUSION: PK/PD parameters -based intermittent intravenous drip dosage regimen of antibiotics designed by means of Excel function is simple,reliable and intuitionistic.

OBJECTIVE:To provide reference for the exploration of training model of clinical pharmacist in according with special condition of our country.METHODS:The manner of clinical pharmacist training and pharmaceutical care in the training base of our hospital were analyzed,and training contents and pattern were summarized.RESULTS&CONCLUSIONS:It needs to improve the capacity of students during clinical pharmacist training in respect of theory and practice.Moreover,strict access system and examination should be strengthened,teaching and studying should complement each other.