Contraindications ; Humans ; Infant ; Infant, Newborn ; Promethazine ; adverse effects

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Acupuncture Therapy ; Adult ; Eye Movements ; Humans ; Male ; Miller Fisher Syndrome ; physiopathology ; therapy

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.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To explore the apoptosis and proliferation of peripheral blood lymphocytes(PBLs) from primary nephrotic syndrome(PNS) and effects of dexamethasone(Dex) on them.Methods Minimal change NS(MCNS), non-minimal change NS(NMCNS) and healthy children were involved in this study. PBLs were cultured in vitro with Dex or PHA+Dex or without PHA and Dex. Apoptosis of PBLs was measured by propidium iodide(PI) staining; The effects of Dex at different concentrons on PBLs′proliferation were investigated by 3H-TdR incorporation.Results The apoptotic rate of vacuity group in MCNS was lower compared with NMCNS and healthy controls(P

Objective To detect mutations of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A (MEN2A). Methods Nineteen family members were recruited in the study. The phenotype of the members with MEN2A were observed. PCR was performed to amplify exans 10 and 11 of the RET proto-oncogene. The PCR products were purified and a direct DNA sequence analysis was performed. Results The Cys (TGC)634Arg(CGC) missense mutation and Gly( GGT)691Ser(AGT) in exon 11 of the RET proto-oncogene were both detected in four members of the family. Only the pelymorphism Gly691Ser in exon 11 of the RET proto-oncogene was detected in one member. The results of the ultrasound examination were shown as follows: two members with bilateral thyroid, one side of parathyroid and adrenal solid lesions; one member with bilateral thyroid and one side of adrenal solid lesions; one member with bilateral thyroid and adrenal and one side of parathyroid solid lesions; and one member with multiple thyroid small nodules. Additionally, another three members with abnormal findings on ultrasound examinations had no gene mutation. Conclusion Analysis of RET gene identifies a TGC to CGC mutation at codan 634 and the polymorphism Gly691 Set in exon 11 in this family with MEN2A. Direct DNA sequencing analysis is useful in diagnosis of MEN2A at gene level.

Objective To investigate the risk factors for postoperative delirium in patients after vascular free flap reconstruction performed under general anesthesia.Methods Two hundred and sixteen ASA Ⅰ-Ⅲ patients aged 18-80 yr undergoing vascular free flap reconstruction surgery were enrolled in this study.Patient characteristics before and during operation were recorded.The patients were followed up for 5 days after operation.Their level of consciousness,severity of pain and sleep quality were evaluated daily.The patients were divided into 2 groups according to the occurrence of delirium during the 5 days after operation:delirium group and non-delirium group.The method of CAM-ICU was reed in the diagnosis of postoperative delirium.Multivariate logistic regression was used to analyze the risk factors for postoperative delirium.Results logistic regression analysis showed that old age,history of alcohol abuse and sleep diacrder after operation were risk factors for delirium developed after free flap surgery.Conclusion Old age,history of alcohol abuse and sleep disorder after operation were the risk factors for postoperative delirium in patients after vascular free flap reconstruction performed under general anesthesia.

OBJECTIVETo investigate the types, clinical features and therapeutic approaches of congenital anomalies of the vagina.

METHODSThe clinical data of 81 patients with congenital anomalies of the vagina were analyzed retrospectively.

RESULTSThere were 5 types in these 81 patients, and 16 (19.7%) patients showed absence of the vagina, 15(18.5%) had vaginal obstruction, 10 (12.3%) had transverse vaginal septum,14(17.2%) had longitudinal vaginal septae,18(22.2%) had septum obliquus, and 8 (9.8%) had imperforate hymen. Forty-eight (59.2%) patients presented with primary amenorrhea, and 22(27.1%) complained of irregular pelvic pain. Fifteen of the patients with absent vagina underwent amnion artificial vaginoplasty, and the others were treated with incising and removing the septum, all having good clinical outcomes.

CONCLUSIONAmnion artificial vaginoplasty is a good option for treatment of absent vagina.

Colpotomy ; methods ; Female ; Gynatresia ; surgery ; Humans ; Reconstructive Surgical Procedures ; methods ; Retrospective Studies ; Vagina ; abnormalities ; surgery

5.5mmol/L),persistent metabolic acidosis,or low cardiac output syndrome.Following data were collected in all patients:time to ni- tiation and duration of PD;time point of the recovery of urine output;baseline serum creatinine level(Cr0),rise of Cr(Crl),peak Cr (Cr2),descending Cr(Cr3),recovery of Cr(Cr4);and their corresponding postoperative time points.Results Of the 63 patients,58 (92.1%)required PD.Overall mortality rate was 33.3%(21/63).Patients undergone more complex surgery requiring longer aortic damping time;have higher Cr0,Cr2,Cr3 and longer period of the recovery of Cr and urine output(P6d)was associated with more complicated surgical procedure,higher Cr1 and Cr2,delayed recovery of Cr and urine output after surgery,longer period of low cardiac output syndrome,more dysfunctional organs,longer mechanical ventilation and ICU stay postoperatively(P