This study aimed at exploring the effects of Griffipavixanthone,a natural small molecule extracted from Garcinia esculenta,on the autophagy and the mechanism behind it.Cervical cancer HeLa cells were selected as the model in vitro.Confocal microscopy,flow cytometry and immunoblotting were performed to know the impacts of Griffipavixanthone on signaling pathway over autophagy flux and calcium level;while nude mouse model was established to explore its anti-cancer action in vivo.It was found that Griffipavixanthone significantly induced GFP-LC3 puncta formation and the accumulation of LC3-Ⅱ/LC3-Ⅰ,and increased the protein expression of SQSTM1 in HeLa cells in a time and concentration dependent manner.MTT assay results showed that Griffipavixanthone inhibited the growth of HeLa cells in a dosage dependent manner,and eliminated the tolerance of tumor cells to nutrient starvation,which fastened the death of cells.Griffipavixanthone also down-regulated the concentration of calcium in the cytoplasm.Furthermore,the in vivo study indicated that intratumoral injection of Griffipavixanthone presented the anti-cancer effect to a certain extent.In conclusion,it was suggested that Griffipavixanthone inhibit autophagy with the potential to be developed into a clinical anti-cancer agent.Griffipavixanthone sensitized HeLa cells to nutrient stress-induced cell death through inhibiting the autophagy flux and the level of calcium in the cytoplasm.

Objective:To observe the effect of combined operation of internal and external surgery for intraocular hemorrhage of polypoidal choroidal vascular disease (PCV).Methods:Retrospective clinical research. From January to August 2018, 14 eyes of 14 patients with PCV combined with vitreous hemorrhage (VH) with hemorrhagic retinal detachment confirmed by eye examination at the Second Affiliated Hospital of Nanchang University were enrolled in this study. The average disease course was 1.12±0.68 months. The visual acuity decreased from 2 to 14 days. The average time from hemorrhagic retinal detachment to surgery was 6.32±2.82 d. There were 9 eyes with BCVA of light sensing, 3 eyes of hand movement, and 2 eyes of counting fingers. The average macular foveal thickness (CFT) was 564.6±102.2 μm. The range of retinal detachment involves equal or greater than 2 quadrants. 23G vitrectomy surgery was used to remove VH, and subretinal hemorrhage was drained through external scleral drainage to reset the retina. One week and 1 and 2 months after the operation, the eyes were injected with 0.05 ml of ranibizumab in the vitreous cavity. The average follow-up time after surgery was 6.24±1.16 months. One week after the operation, 1, 3, and 6 patients were examined with the same equipment and methods before the operation to observe the condition of BCVA, CFT, intraocular pressure and retinal reattachment. Non-parametric tests were used to compare BCVA before and after surgery.Results:VH was completely cleared in all eyes, and no iatrogenic retinal hole appeared during the operation. Six months after the operation, there were 1 eye with BCVA of hand movement, 1 eye of counting fingers, 8 eyes of 0.1, 2 eyes of 0.2 and 2 eyes of over than 0.2; the average CFT was 336.4±54.8 μm. Compared with before surgery, the BCVA was significantly improved ( Z=-3.711, P=0.000), the CFT was significantly decreased ( t=3.212, P=0.006). OCT examination showed that the macular morphology and structure were clearly visible. Of the 14 eyes, 13 eyes were reattached, 1 eye was detached again after silicone oil removal. Intraocular pressure increased in 3 eyes within 1 week after surgery, including 1 eye with a small amount of blood in the anterior chamber. No recurrent VH was found in all eyes during follow-up. Conclusions:Combined internal and external surgery for PCV combined with VH with hemorrhagic retinal detachment is safe and effective.

Objective The aim of this study was to investigate the mechanism of sanguinarine(SANG)on the inhibitory pro-liferation in ovarian cancer SKOV3 cells. Methods CCK-8 assay was used to detect proliferation of SKOV3 cells. Flow cytometry was used to detect the effect of SANG on apoptosis in SKOV3 cells. The spectrophotometer was used to detect the production of reac-tive oxygen species(ROS)by SANG. The mouse ovarian cancer xenograft model was used to detect the inhibitory effect of SANG on tumor growth. Results SANG promoted apoptosis in SKOV3 cells in a dose-and time-dependent manner. The SANG-induced ap-optosis was associated with the production of ROS,Activated the c-Jun-N-terminal kinase( JNK) and nuclear factor-κB( NF-κB)signaling pathways. In mouse model of ovarian cancer xenografts,after intravenous injection of mice with SANG,SANG was signifi-cantly inhibited the growth of ovarian cancer xenografts when compared to the control group. SANG also significantly induced apoptosis in ovarian cancer xenografts. Conclusion SANG can significantly inhibit the proliferation of ovarian cancer SKOV3 cells,induce ap-optosis,increase the production of ROS,and inhibit the growth of ovarian cancer.

OBJECTIVETo assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification (MLPA) as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects.

METHODSThe combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis (CMA).

RESULTSNineteen (18%) fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations (CNVs) and 4 CNVs of uncertain significance (VOUS). MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV.

CONCLUSIONCombined use of G-banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.

Chromosome Aberrations ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Testing ; methods ; Heart Defects, Congenital ; diagnosis ; genetics ; Humans ; Karyotyping ; methods ; Multiplex Polymerase Chain Reaction ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Sensitivity and Specificity

Objective:To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression.Methods:The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected.Results:The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive ( P<0.001), Ki-67 index below 35% ( P<0.001), well or moderate differentiation ( P<0.001) and over the age of 50 ( P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions:The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.