[Clinical Analysis of 269 Ph Chromosome-Negative Myeloproliferative Neoplasms Patients Stratified by Age].

OBJECTIVE: To investigate the difference of clinical characteristics between young patients(age≤40 years old) and middle-older patients(age>40 years old) with the myeloproliferative neoplasms（MPN）. METHODS: The clinical data (gene mutations， peripheral blood routine examinations， imaging examination and past history) of 269 MPN patients was collected and analyzed. RESULTS: In essential thrombocythemia (ET) group, the proportion of triple-negative type in young patients was higher than that in middle-older group, while the peripheral white blood cell（WBC） and platelets（PLT） counts in the first visit were lower. In polycythemia vera (PV) group, the total detection rate of JAK2V617F (80.65%) was lower than that of other research reports. Young patients with PV showed the lower JAK2V617F rate and lower WBC count, compared with the middle-older aged patients. Both CALR and MPL mutations were not found in PV patients. There was only 1 primary myelofibrosis (PMF) patient aged <40 years old. 91.67% of the patients merged splenomegaly and this rate was higher than that of ET or PV patients. It was found that there were a diagnosed familial MPN family and an undiagnosed family， and the youngest patient was only 8 years old. The second-generation gene sequencing detection for them was not carried out. CONCLUSION: Age is an important reference index in the assessment of risks. The MPN patients with different age and types show much difference in gene mutations, peripheral blood cell counts, thrombotic events and sizes of spleen. The onset ages of patients with familial MPN trends to be generational younger.

Synthesis and fungicidal activity of macrolactams and macrolactones with an oxime ether side chain.

Three series of novel macrolactams and macrolactones--12-alkoxyimino-tetradecanlactam, 12-alkoxyiminopentadecanlactam, and 12-alkoxyiminodecanlactone derivatives (7A, 7B, and 7C)--were synthesized from corresponding 12-oxomacrolactams and 12-oxomacrolactone. Their structures were confirmed by 1H NMR and elemental analysis. The Z and E isomers of 7A and 7B were separated, and their configurations were determined by 1H NMR. These compounds showed fair to excellent fungicidal activities against Rhizoctonia solani Kühn. It is interesting that the Z and E isomers of most of the compounds have quite different fungicidal activities. The fact that the compounds have a gradual increase of fungicidal activity in the order of 7A, 7C, and 7B indicated that the macrocyclic derivatives with a hydrogen-bonding acceptor (=N-O-) and a hydrogen-bonding donor (-CONH-) on the ring, and a three methylenes distance (CH2CH2CH2) between these two functional groups, exhibited the best fungicidal activity. The bioassay also showed that 7B not only has good fungicidal activity but also may have a broad spectrum of fungicidal activities.

The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction undergoing emergent PCI.

The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction (AMI) undergoing emergent percutaneous coronary intervention (PCI) was estimated. One hundred and twenty-eight patients were randomly divided into control group and observation group with 64 cases in each group. Control group adopted routine blood coagulation indexes, including prothrombin time, activated partial thromboplastin time, fibrinogen and plasma thrombin time, platelet count and platelet aggregation turbidity analysis; observation group adopted Sonoclot detection technology, including activated clotting time, coagulation rate and platelet function. Anticoagulant therapy selected was of low molecular weight heparin calcium perioperatively, intraoperative unfractionated heparin, and clopidogrel (75 mg) combined with aspirin enteric-coated tablets (100 mg) as antiplatelet drugs. The therapy was administered in accordance with blood coagulation results. The blood coagulation time, postoperative creatine kinase isoenzyme MB, cardiac troponin I and B-type natriuretic peptide levels in the observation group are significantly lower than those in the control group (P<0.05) though the operating time and specifications of the stenting did not show any significant difference (P>0.05). The incidence of recurrent myocardial infarction, microembolism, acute and subacute thrombosis and bleeding events in the observation group are significantly lower than those in the control group (P<0.05). In the control group, there is no difference in the coagulation indexes of the patients with thrombosis events or bleeding events or no event (P>0.05). Whereas, in the observation group, there is significant difference in coagulation indexes of the patients with thrombosis events or bleeding events or no event (P<0.05). In conclusion, Sonoclot detection technology instructs emergent PCI treatment in AMI patients to shorten the detection time of blood coagulation, reduce the degree of myocardial injury, reduce the incidence of perioperative thrombosis and bleeding events. Furthermore, it has great value in guiding the clinical medication of anticoagulation and antiplatelet therapy.

Synthesis and fungicidal activity of novel 2-oxocycloalkylsulfonylureas.

A series of 2-oxocycloalkylsulfonylureas (2) have been synthesized in a six-step, three-pot reaction sequence from readily available cyclododecanone, cycloheptanone, and cyclohexanone. Their structures were confirmed by IR, 1H NMR, and elemental analysis. The bioassay indicated that some of them possess certain fungicidal activity against Gibberella zeae Petch. In general, compounds containing a 12-membered ring (2A) are more active than those containing a 6- or 7-membered ring (2B, 2C). In the series 2A, the compounds in which R is a disubstituted phenyl or pyrimidyl showed better activity than those in which R is a monosubstituted phenyl or pyrimidyl, and aryl-substituted compounds have somewhat higher activity than those substituted by pyrimidyl. The further bioassay showed that the representative of 2A, 2A15, has good fungicidal activities against not only G. zeae Petch but also Botrytis cinerea Pers, Colletotrichum orbiculare Arx, Pythium aphanidermatum Fitzp, Fusarium oxysporum Schl. f. sp. Vasinfectum, etc.

Synthesis, fungicidal activity, and structure-activity relationship of spiro-compounds containing macrolactam (macrolactone) and thiadiazoline rings.

Two series of novel spiro-compounds containing macrolactam or macrolactone and thiadiazoline rings, 1-thia-2-alkylimino-3,4,9-triaza-10-oxospiro[4.15]eicosyl-3-ene (4F) and 1-thia-2-alkylimino-3,4-diaza-9-oxa-10-oxospiro[4.15]eicosyl-3-ene (4G), were synthesized from 12-oxo-1,15-pentadecanlactam and 12-oxo-1,15-pentadecanlactone, respectively. Their structures were confirmed by elemental analysis, (1)H NMR, and (13)C NMR. The conformation of compounds 4F was determined via the crystal structure of a representative compound (4F(6)). The bioassay showed that compounds 4F have much better fungicidal activity against five fungi ( Botrytis cinerea Pers., Sclerotinia sclerotiorum , Rhizoctonia solani Kuhn., Phomopsis asparagi Sacc., and Pyricularia oryzae Cav.) than compounds 4G. The fact above showed that the presence of a hydrogen-bonding donor for the fungicidal activity of macrocyclic compounds is very important. 4F(6) showed excellent fungicidal activity against P. oryzae, which is much better than the commercial fungicide isoprothiolane, and 4F(13) showed excellent fungicidal activity against P. oryzae and good fungicidal activity against P. asparagi.

Synthesis and herbicidal activity of 12-(aryloxyacyloxyimino)-1,15-pentadecanlactone derivatives.

A series of novel 12-(aryloxyacyloxyimino)-1,15-pentadecanlactone derivatives (3) were synthesized, and their structures including configuration of C=N bond were confirmed by (1)H NMR, elemental analysis and X-ray diffraction analysis. The bioassay showed that some of them exhibited excellent herbicidal activity against Amaranthus tricolor L. The activity of compounds 3 except compounds 3A1-2 was much higher than the commercial herbicide 2,4-D and the activity of about half of compounds 3 was comparable to the commercial herbicide tribenuron-methyl. The further bioassay showed that the representative of compounds 3, 3A1-12, exhibited excellent herbicidal activity not only against dicotyledon, such as Amaranthus tricolor L., Cucumis sativus L., Glycine max L., and Phaseolus radiatus L., but also against monocotyledon, such as Zea mays L. and Oryza sativa L.

Design, synthesis, and fungicidal activity of macrolactones and macrolactams with a sulfonamide side chain.

Four series of novel macrolactones and macrolactams12-alkylsulfonamido-1,15-pentadecanlactones ( 5), 12-alkylsulfonamido-15-methyl-1,15-pentadecanlactones ( 6), 12-alkylsulfonamido-1,15-pentadecanlactams ( 7), and N-(alkylsulfonamidoethyl)-1,12-dodecanlactams ( 8)were designed and synthesized from readily available 2-nitrocyclododecanone or cyclododecanone. Their structures were confirmed by (1)H NMR, IR, and elemental analysis. The bioassay showed that these compounds displayed fair to excellent fungicidal activity against Rhizoctonia solani Kuhn and have a gradual increase of fungicidal activity in the order of 6, 7, 8, and 5. Among them, compounds 5a, 5b, and 5c displayed excellent fungicidal activity against R. solani comparable with the commercial fungicide carbendazim. Above results illustrated that the rule on the relationship between the activity and hydrogen-bonding, namely the macrocyclic compounds with a hydrogen-bonding acceptor and a hydrogen-bonding donor on the ring and having a three methylenes distance between two polarizable groups have the best fungicidal activity against R. solani, has a general suitability to the macrocyclic compounds, and pesticide molecules may combine with a target enzyme by hydrogen-bonding. The facts, which compound 6 has a much lower fungicidal activity against R. solani than compound 5 but their difference in chemical structure is only that there is a methyl group on the C15 for compound 6 and none but hydrogen atom on the C15 for compound 5, indicated that a methyl group plays an inhibitory role to the fungicidal activity. It suggests that the existence of a methyl group with a great volume between two polarizable groups would interfere in the interaction of pesticide molecules and the target enzyme.