Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.

Objective To find an ideal liver cirrhosis portal hypertension model in big animals suitable for surgical study.Methods Twenty canines were treated by subcutaneous injection of 60% CCl4 colza oil emulsion into the back,at a dose of 1.0-1.3 mL/kg every 10 days for a total of 6-8 times.At the same time,it was combined with the control of food intake.All canines were fed with rice mixed with 10% hog fat.The amount of rice was 15 g/kg per day from the first day to the forth day,but the amount of food was not controlled from the fifth day to the tenth day.During the process,the canines′ general condition was observed and the changes of hepatic functions such as ALT,TP,ALB,G and A/G were measured.The changes of liver morphology,the diameter and blood flow of portal vein were monitored with color Doppler.Every two weeks,a piece of hepatic tissue to observe the pathological change of liver was excised operatively.Results During the process,the body weight of the canines decreased continually;ALT increased during early and middle stages and decreased during advanced stage;TP and ALB always decreased,and A/G continuously decreased,but G did not change significamtly.Eight weeks after injection,liver became progressively smaller.its density was not well-distributed,and liver particles gradually became coarse,and liver capsule became rough.The diameter of portal veins became larger and the velocity of portal vein became slower.Liver cirrhosis with psudolobules was found on light microscopy from the tenth week to the twelfth week.Three canines died,with mortality of 15.0%.Conclusions It took 10-12 weeks to establish this liver cirrhosis portal hypertension models in canines by subcutaneous injection of CCl4.This method is convenient,has high success rate,and is suitable for use in surgieal research.

A 20-year-old male patient presented with myalgia of upper limbs and myasthenia of extremities for more than 1 month. Physical examination showed diffuse erythema on the cheeks, upper eyelids, upper chest, neck and dorsa of the hands. The myodynamia of the proximal and distal muscles of upper and lower extremities was grade Ⅳ, Ⅴ, Ⅲ and Ⅴ respectively. Laboratory examinations revealed that the serum levels of creatine kinase, CK-MB and lactate dehydrogenase were 2103 U/L, 83 U/L and 489 U/L respectively, which were all above the normal range. Electromyogram revealed myopathic abnormality and normal nerve conduction velocity. Histopathology of gastrocnemius muscle showed hypertrophy and swelling of muscle fibers, disappearance or fuzziness of transverse striation, and intermuscular lymphoid cell infiltration. A biopsy of the skin lesion from the upper chest showed liquefaction degeneration of and colloid bodies in basal cell layer, perivascular lymphoid cell infiltration in the dermis. A diagnosis of dermatomyositis was established based on the clinical and laboratory findings. After management with intravenous prednisolone 80 mg once daily and symptomatic treatment for 4 weeks, the myodynamia of upper limbs was improved, serum levels of creatine kinase,CK-MB and lactate dehydrogenase reached the normal ranges. However, the myodynamia of lower limbs progressively deteriorated with the emergence of paresthesia. Enhanced MRI scan showed a tumor in the vertebral canal at the level of thoracic vertebra 11 to 12. A spherical encapsulated tumor measuring 3 cm in diameter was surgically removed. The tumor was diagnosed as paraganglioma in vertebral canal according to pathological and immunohistochemical findings. The patient was finally diagnosed with paraganglioma in vertebral canal superimposed on dermatomyositis.

OBJECTIVE: To obtain the genetic polymorphism data of two STR loci D2S1399 and D5S2500 in Eastern Chinese Han population. METHODS: Blood samples or buccal swabs of unrelated Han individuals living in eastern China were analyzed using PCR-nature polyacrylamide gel electrophoresis-sliver staining method. RESULTS: 11 alleles of D2S1399 and 9 alleles of D5S2500 were observed in the samples respectively, the observed heterozygosity (Ho) values, the discrimination power (DP) values and the power of exclusion (PE) values of D2S1399 and D5S2500 is 0.745 and 0.807, 0.958 and 0.917, 0.554 and 0.643, respectively. CONCLUSION The result showed that D2S1399 and D5S2500 were highly informative loci and suitable for forensic application.
Alleles ; Asian People/genetics* ; Electrophoresis, Polyacrylamide Gel ; Forensic Medicine ; Gene Frequency ; Genetics, Population ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Silver Staining ; Tandem Repeat Sequences

OBJECTIVETo determine the efficacy and safety of oral caffeic acid (CA) tablet in management of primary immune thrombocytopenia(ITP).

METHODSOne hundred and three ITP patients with PLT>10×10⁹/L and no serious bleeding symptoms from three centers were enrolled. According to their platelet count before CA treatment, these patients were divided into group A (PLT<30×10⁹/L), including 24 females and 27 males with median age 48(18-84)years; and group B (PLT≥30×10⁹/L), including 33 females and 19 males with median age 43(18-83)years. Patients in both groups took CA tablets orally of 300 mg three times per day for 12 consecutive weeks. Combined medicine treatment such as corticosteroids, danazol, TPO and Rituximab, which might increase the platelet count of these patients, were not allowed during CA therapy.

RESULTSIn group A, the overall response rate was 51.0%(26/51), with 2 patients achieving complete response (CR) and 24 patients achieving response(R). Of 26 patients achieving response (CR+R), the median platelet count before CA therapy was 20.5(15-28)×10⁹/L , and the median peak platelet count after CA therapy was 63(38-112)×10⁹/L. The median time to achieving response was 4(2-10) weeks. Patients with pretreatment PLT>20×10⁹/L showed significantly better response than those PLT<20×10⁹/L (68.0% vs 34.6%, P=0.017). In group B, the CR rate was 40.4%(21/52). Frequency of CA-related adverse events was 1.94%(2/103), including mild nausea in 1 case and elevation of liver enzymes in 1 case. Both were grade 1 and transient.

CONCLUSIONCaffeic acid was effective in patients with ITP with few and mild adverse effects.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; Caffeic Acids ; Female ; Glucocorticoids ; Humans ; Male ; Middle Aged ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Remission Induction ; Rituximab ; Tablets ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the early hematologic, cytogenetic and molecular responses in newly diagnosed patients with chronic myelogenous leukemia in chronic phase（CML-CP）and initially treated with a generic imatinib（Xinwei）, manufactured by Jiansu Hansoh Pharmaceutical Group Co., Ltd.

METHODS107 newly diagnosed patients of CML-CP, whose ages were above 18- year- old and who had never received any tyrosine kinase inhibitor（TKI）were treated with Xinwei 400 mg QD. The hematologic, cytogenetic and molecular responses were assessed at 3- and 6-month, and adverse effects were evaluated throughout the study.

RESULTS107 patients were treated with Xinwei for at least 3 months, 54 of them were treated for 6 months or more. At 3- month, the complete hematologic responses（CHR）rate were 98.1%（105/107）; 47/57（82.5%） patients achieved major cytogenetic response（MCyR）, and 20/57 （35.1%） patients complete cytogenetic response（CCyR）; BCR- ABLIS was ≤10% in 77/106 patients （72.6%）, 11 of them（10.4%）achieved major molecular response（MMR, BCR-ABLIS was ≤0.1%）. At 6-month, the CHR rate was 100%（54/54）; 28/39 patients（71.8%）achieved CCyR; BCR-ABLIS was ≤1% in 37/54 patients （68.5% ）, 18 of them （33.3% ） achieved MMR. The grade Ⅲ leukopenia, thrombocytopenia and anemia rates were 19.5%, 23.0% and 13.8%, respectively. No grade Ⅳ hematologic toxicity occurred. The common non- hematologic toxicities were edema（74.7%）, nausea（48.3%）, bone pain（42.5%）, rash（36.8%）, diarrhea（34.5%）, fever（23.0%）, cramp（11.5%）and impaired liver function （3.4%）. No patient experienced grade Ⅳ non- hematologic toxicity. No adverse effects related death occurred.

CONCLUSIONOur results revealed the excellent early haematology, cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP.

Anemia ; Antineoplastic Combined Chemotherapy Protocols ; Cytogenetics ; Drugs, Generic ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Prospective Studies ; Protein Kinase Inhibitors ; Remission Induction ; Thrombocytopenia ; Treatment Outcome

Objective:To explore the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease(COVID-19).Methods:The clinical diagnosis and treatment of one living-related kidney transplant recipient after the occurrence of COVID-19 were analyzed retrospectively. Course of onset, clinical manifestations, laboratory and image enamination, outpatient and inpatient therapies and outcomes.Results:The renal transplant recipient was diagnosed as COVID-19(severe) with influenza A virus infection based upon epidemiological survey, clinical manifestations, laboratory examinations, imaging findings and etiological tests. The clinical symptoms were gradually relieved and lung lesions became absorbed after tapering and withdrawing immunosuppressants, antiviral therapy of abidol/oseltamivir, antibiotic therapy, hormonal anti-inflammation, oxygen inhalation, nutritional supports and adequate rest.Conclusions:Living-related kidney transplant recipients have specific immunosuppressive states.The long-term effect of covid-19 on recipients should be determined through long-term follow-ups.

Objective: To analyze the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease (COVID-19) . Method: The clinical diagnosis and treatment of one relative renal transplant recipient after the occurrence of COVID-19 were analyzed retrospectively, including the course of onset, clinical manifestations, blood routine test, renal function, lung CT scan, nucleic acid detection, outpatient and inpatient therapies and outcomes. Result: The case was diagnosed as COVID-19 (severe type) with influenza A virus infection. The clinical symptoms were gradually relieved and the lung lesions were absorbed through the treatment of reduce and stop taking immunosuppressant, antiviral therapy of abidol/oseltamivir, prevention of bacterial infection, hormone anti-inflammatory, oxygen inhalation, nutritional support and adequate rest. Conclusion This case present typical characteristics of COVID-19 in epidemiological investigation, clinical manifestation, examination, pulmonary imaging and etiology. After comprehensive treatment including reduce and stop immunosuppressive therapy, clinical cure was achieved. The long-term effect of COVID-19 on this immunosuppressive patient remains follow-up.