BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Objective: To compare the value of two 3D imaging reconstruction methods for left atria and pulmonary vein on guiding the catheter ablation for atrial fibrillation (AF). Methods: From January 2014 to January 2017, a total of 100 drug refractory paroxysmal AF patients were divided into left atria direct angiography group (n=50), and indirect angiography group (n=50). 3D CARTO system was applied for mapping and guiding the ablation procedure. Patients assigned to direct angiography group were treated as follows: intraoperative puncture of atrial septum, inject contrast agent directly into the left atrium, conduct left atrial and pulmonary venous rotation angiography, reconstruct three-dimensional image, integrate the image into real-time X-ray system to facilitate circumferential pulmonary vein isolation. Patients assigned into the indirect angiography group were treated as follows: inject contrast agent through the right ventricle, conduct delayed rotation angiography of the left atria and pulmonary vein to guide circumferential pulmonary vein fixation and ablation. The left atrial and pulmonary venous image acquisition, the operation and X-ray exposure time, the success rate and the incidence of complication of the two groups were compared. The patients were followed up for 3-6 months. Results: General clinical characteristics of the two groups were similar(all P>0.05). Ablation was successful in all 100 patients. The operation time[(112.0±21.4)min vs. (134.0±24.3)min]and X-ray exposure time((10.7±4.7)min vs. (15.8±5.2)min)were significantly lower in direct angiography group than in indirect angiography group (both P<0.01). There was no significant difference between the two groups in the immediate (86%(43/50) vs. 82%(41/50), P=0.59) and short-term (76%(38/50) vs. 72%(36/50), P=0.65) success rate and complication rate (1 aneurysm in the direct angiography group, 1 pericardial tamponade in the indirect angiography group). In-hospital mortality was zero percent. Conclusion It is safe and effective method to guide the radiofrequency catheter ablation of paroxysmal atrial fibrillation by reconstruction 3D image of left atrium and pulmonary vein. Compared with indirect angiography group, direct angiography group can improve the imaging quality of left atrium and pulmonary vein, decrease the X-ray exposure time of the ablation procedure.

Objective To investigate the protection effect of dexmedetomidine against H2O2 injury in Human renal tubular epithelial cells(HK-2 cells). Methods HK-2 cells cultured in vitro were randomly divided into four groups(n = 24): control group, dexmedetomidine pretreatment group, H2O2 injury group, H2O2 injury +dexmedetomidine pretreatment group. Cell viabilities were measured by MTS assay, cell apoptosis were detected using flow cytometry, and expression of HIF-1α protein was quantified by western blot. HK-2 cells were divided into 8 groups by combining with three treatment factors such as PI3K inhibitor LY294002, dexmedetomidine and H2O2 injury. MTS assay was used to detect cell viability and western blot was used to quantify protein expression of HIF-1α,Bcl-2 and Bax after treatment in each group. Results Dexmedetomidine significantly increased the level of HIF-1α、 Bcl-2 in HK-2 cells after H2O2 injury, thus improved viabilities and reduced apotosis of cells. Moreover, effect on H2O2 injury cells of Dexmedetomidine was reversed by PI3K inhibitor LY294002. Conclusion Dexmedetomidine could protect against H2O2 injury by up-regulating HIF-1α expression through activating PI3K/Akt/mTOR signaling pathway in HK-2 cells.

Objective To evaluate the role of mammalian target of rapamycin (mTOR) signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion (I/R) injury in rats and the relationship with hypoxia-inducible factor 1 (HIF-1α).Methods Seventy-two male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were randomly divided into 4 groups (n=18 each) using a random number table: sham operation group (group S), group I/R, dexmedetomidine group (group Dex) ,and rapamicyn + dexmedetomidine group (group Rpm+Dex).Renal I/R was produced by occlusion of bilateral renal pedicles for 35 min follow by reperfusion in anesthetized rats in I/R, Dex and Rpm+Dex groups.Bilateral renal pedicles were only exposed, and then the abdominal cavity was closed in group S.Dexdetomidine 50 μg/kg was injected intraperitoneally at 30 min before I/R in group Dex.In group Rpm+Dex, rapamicyn 1.5 mg/kg and dexdetomidine 50 μg/kg were injected intraperitoneally, and renal I/R model was established 30 min later.Immediately after onset of reperfusion, and at 4 and 24 h of reperfusion (T1-3) , blood samples were collected from the caudal vein for measurement of serum creatinine and blood urea nitrogen (BUN) concentrations.After blood sampling at T1-3, the rats were sacrificed, and the renal specimens were obtained for detection of HIF-1αt, erythropoietin (EPO) and mTOR expression by Western blot.Their kidneys were removed at T3, and cut into sections which were stained with haematoxylin and eosin and examined under microscope.Acute renal tubular necrosis was scored.The cell apoptosis in renal tissues was detected by TUNEL assay, and apoptosis index (AI) was calculated.Results Compared with group S,the concentrations of serum creatinine and BUN, expression of HIF-1α, EPO and mTOR at T2,3 , AI at T3 and acute renal tubular necrosis score were significantly increased in the other three groups (P＜ 0.05).Compared with group I/R, the concentrations of serum creatinine and BUN were significantly decreased, and the expression of HIF-1α, EPO and mTOR was up-regulated at T2,3 , and AI and acute renal tubular necrosis score were decreased in group Dex (P＜0.05) , and no significant change was found in the parameters mentioned above in group Rpm + Dex (P ＞ 0.05).Conclusion The mTOR signaling pathway is involved in dexmedetomidine-induced reduction of renal I/R injury, which may be related to dexmedetomidine-produced up-regulation of HIF-1α expression in renal tissues of rats.

Objective To investigate the effects of ginkgolide B on neuronal cell apoptosis,superoxide dismutase activity,malondialdehyde,interleukin-1beta,tumor necrosis factor-alpha,and interleukin-6 levels in serum of rats with intracerebral hemorrhage in order to explore the role of ginkgolide B in suppressing the neuronal cell apoptosis.Methods A total of 175 male Wistar rats were randomly (random number)divided into sham operation group,intracerebral hemorrhage group,as well as low,medium and high dose treatment groups.The rat model of intracerebral hemorrhage was made with infusion of autologous whole blood to caudate nucleus in the right basal ganglia region.Ginkgolide B in dose of 5 mg/kg,10 mg/kg and 20 mg/kg was given to rats in the low,middle and high dose treatment groups by intraperitoneal injection once a day for 5 days after intracerebral hemorrhage.The rats with intracerebral hemorrhage in the sham operation groups received intraperitoneal administration of 1 mL saline.Animals were sacrificed by decapitation 2,6,12,24,48,72 h and 5 days after intracerebral hemorrhage.Brains were taken and blood samples were collected.Neuronal cell apoptosis was measured by using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling(TUNEL),and superoxide dismutase activity in serum was determined by using xanthine oxidase method,and serum malondialdehyde level was detected by using thiobarbituric acid reactive substance assay,and interleukin-1beta,tumor necrosis factor-alpha,and interleukin-6 levels in serum were assayed with enzyme linked immunosorbent assay(ELISA).Statistical analysis was carried out by using one-way analysis of variance and least-significant difference test.Results As 2 h,6 h,12 h,24 h,48 h,72 h,and 5 days after intracerebral hemorrhage,the differences in the number of apoptotic neuronal cell,superoxide dismutase activity in serum,serum malondialdehyde,interleukin-1 beta,tumor necrosis factor-alpha and interleukin-6 levels between the low dose treatment group and intracerebral hemorrhage group were not significant statistically(P ＞0.05).As 12 h,24 h,72 h,and 5 days after intracerebral hemorrhage,the number of apoptotic neuronal cell,superoxide dismutase activity in serum,serum malondialdehyde,interleukin-1 beta,tumor necrosis factor-alpha and interleukin-6 levels in the medium dose and high dose treatment groups were significantly statistically lower than those in the intracerebral hemorrhage group(P ＜ 0.05),but these differences in above biomarkers were not significant statistically among these three groups 2 and 6 hours after intracerebral hemorrhage(P ＞ 0.05).Conclusions Ginkgolide B may lessen neuronal cell apoptosis by means of inhibition of free radical production and inflammatory reactions after intracerebral hemorrhage.

Objective To investigate the relationship between serum progesterone level at the day with human chorionic gonadotrophin (hCG) administration and pregnant outcome from in in-vitro fertilization-embryo transfer(IVF-ET). Methods From Mar. 2002 to Apr. 2007, 786 cycles with serum progesterone measurement on the day of hCG administration for final oocyte maturation in IVF were analyzed retrospectively in Reproductive Medicine Center in First Affiliated Hospital of Nanjing Medical University.All stimulations were down-regulated with gronadotrophin release hormone agonist (GnRH-a) in both long protocols and short protocols before gonadotrophin stimulation. When the thresholds of serum progesterone were set at 5.5, 6.0,6.5,7.0,7.5,8.0,8.5 and 9.0 nmol/L, respectively. If the level of progesterone was less than the thresholds, those patients were in lower progesterone group, on the contrary, more than the threshold value, those patients were in higher progesterone group. The laboratory results and the clinical outcomes between all patients at lower and higher progesterone group at different thresholds value were analyzed. Results The rate of normal fertilization, quality embryos, successful implantation, chemical pregnancy, clinical pregnancy and live birth did not exhibit remarkable difference between patients with higher and lower serum progesterone level at multiple thresholds on the day of hCG administration in the 786 cycles (P >0.05). However, when the thresholds of serum progesterone were at 8.5 and 9.0 nmol/L, early abortion rates of 27.3% (3/11) and 3/7 in higher progesterone group were significantly higher than 8.8% (26/297) and 8.6% (26/301) in lower progesterone group (P<0.05). And the total abortion rates of 3/7 in higher progesterone group were significantly higher than 11.0% (34/301) in lower progesterone group when the thresholds of serum progesterone were 9.0 nmol/L (P<0.05). Conclusions This study did not prove the correlationship between progesterone level at the clay with hCG administration and the probability of clinical pregnancy or live birth. However, early abortion rates or the total abortion rates were associated with higher progesterone level when the thresholds of serum progesterone were at 8.5 nmol/L or 9.0 nmoL/L.

Objective To develop a rapid,reliable and convenient approach for diagnosing the homozygous deletion of SMN1 gene.Methods SMN1 gene was amplified specifically with double allele-specific PCR(AS-PCR).Meanwhile,one inrelevant gene was amplified as internal control by PAGE and agarose gel electrophoresis analysis to determine whether the sick children were with homozygous deletion of SMN1 genes.Results The homozygous deletion of exon7 in SMN1 gene was identified by agarose gel electrophoresis or PAGE accurately.Conclusion Compared to PCR-RFLP and DHPLC used in the past,this approach can diagnose homozygous deletion of SMA much more accurate,easier and more convenient without completed following analyses.

Objective To discover the mutation of ADAR gene in a pedigree with dyschromatosis symmetrical hereditaria(DSH). Methods We investigated this family and collected blood samples of the individuals in this family. Mutation screening was carried out by PCR and direct sequencing. The allele specific primer was designed for the mutation point, and allele-specific PCR was carried out on the patients, normal family members and 40 normal individuals. Results A single nucleotide deletion (c.1642 delC) was identified in exon3 of ADAR gene in the patients of this family. This mutation was not detected in the normal family members and in any of the control individuals. Conclusion This single nucleotide deletion was responsible for the disease in the family.