Objective:To characterize the geriatric osteoporotic pelvic fractures using 3-D computed tomography (CT) fracture mapping.Methods:Retrospectively analyzed were the 79 elderly patients with pelvic fracture who had been admitted to Department of Orthopaedics, The 7th Medical Center of PLA General Hospital between January 2017 and December 2021. There were 24 men and 55 women, aged from 60 to 98 years (average, 74.3 years). The CT scan data of the pelvis from all patients were imported into the software (Mimics Medical 18.0, Geomagic Studio 2014, Rhinoceros 6.0, and Matlab) to create a 3-D pelvic fracture model. The fracture pieces were imported into a standard pelvic template to obtain the morphology of the fracture lines after fitting. A map of fracture line distribution frequency and a fracture heat map were created by fitting the fracture lines of all patients into a common pelvic template.Results:Of the 79 elderly patients with pelvic fracture, 69 (87.3%) had fractures of both the anterior and the posterior rings. The fracture map and heat map of geriatric pelvic fractures showed the following: the fracture lines of the anterior ring were concentrated in the junction of the cancellous bone and cortical bone of the superior and inferior pubic rami; the fracture lines of the posterior ring were concentrated in the middle and posterior 1/3 of the ilium and in the sacral wing; the fracture frequencies incurred by the pubic bone, sacrum, and ilium were from the highest to the lowest.Conclusions:Fracture mapping can visually characterize the distribution of fracture lines of the geriatric pelvic fractures. Simultaneous fractures of the anterior and posterior rings of the pelvis are the most typical kind of pelvic fractures in the elderly. The junction of the cancellous and cortical bones of the superior and inferior pubic rami and the area surrounding the sacroiliac joint are the most frequent locations for the fractures.

Objective : To investigate the effect and mechanism of miR⁃145 ⁃3p on mitophagy in 1 ⁃methyl⁃4 ⁃pheny⁃lpyridiniumion ( MPP + ) Ⅳinduced Parkinson ′ s disease ( PD) cell model . Methods : Human neuroblastoma cells SH⁃SY5Y) were divided into control group , model group , mimics group , calmodulin⁃dependent protein kinase kinaseβ (CaMkkβ) inhibitor ( STO⁃609) group , mimics + STO⁃609 group , cyclic adenosine monophosphate response element⁃binding protein (CREB) inhibitor (KG⁃501) group , mimics + KG⁃501 group and STO⁃609 + KG⁃501 group . Cell apoptosis was detected by flow cytometry , autophagosome structure was observed by transmission electron microscopy , and apoptosis , autophagy and CaMkkβ/adenylate activated protein kinase ( AMPK) /CREB pathway related protein expression were detected by Western blot . Results : Compared with control group , the apoptosis rate , Bcl⁃2 ⁃associated X protein (Bax) , cysteine proteinase⁃3 (Caspase⁃3) and microtubule⁃associated protein light chain 3 ⁃I (LC3 ⁃ Ⅰ ) protein expression levels in model group increased (P < 0. 01) , and the autophagosome structure decreased . The protein levels of B cell lymphoma⁃2 (Bcl⁃2) , autophagy gene (Beclin⁃1) , microtubule⁃associated protein light chain 3 ⁃ Ⅱ ( LC3 ⁃ Ⅱ ) , phosphorylated calmodulin⁃dependent protein kinase kinaseβ(p⁃CaMkkβ) , phosphorylated cadenylate activated protein kinase ( p⁃AMPK) , and phosphorylated cyclic adenosine monophosphate response element⁃binding protein ( p⁃CREB) decreased ( P < 0. 01) . Compared with model group , the apoptosis rate , Bax , Caspase⁃3 and LC3 ⁃ Ⅰ protein expression levels in mimics group decreased (P <0. 05 ) , and the autophagosome structure increased . The protein levels of Bcl⁃2 , Beclin⁃1 , LC3 ⁃ Ⅱ , p ⁃CaMkkβ , p ⁃AMPK , p ⁃CREB increased (P < 0. 05) . The trend of STO⁃609 group and KG⁃501 group was the same and opposite to mimics group . Compared with mimics group , the apoptosis rate , Bax , Caspase⁃3 and LC3 ⁃ Ⅰ protein expression levels in the mimics + STO⁃609 group and the mimics + KG⁃501 group increased (P < 0. 01) , and the autophagosome structure decreased . The protein levels of Bcl⁃2 , Beclin⁃1 , LC3 ⁃ Ⅱ , p ⁃CaMkkβ , p ⁃AMPK , p ⁃CREB protein levels decreased (P < 0. 01) . Compared with STO⁃609 group , the apoptosis rate , Bax , Caspase⁃3 and LC3 ⁃ Ⅰ pro⁃tein expression levels of STO⁃609 + KG⁃501 group increased ( P < 0. 01) , and the autophagosome structure decreased . The protein levels of Bcl⁃2 , Beclin⁃1 , LC3 ⁃ Ⅱ , p ⁃CaMkkβ , p ⁃AMPK and p ⁃CREB decreased ( P <0. 05) . Conclusion miR⁃145 ⁃3p can inhibit the apoptosis of MPP + Ⅳinduced PD cell model and promote mitophagy , and its mechanism may be related to the activation of the CaMkkβ/AMPK/CREB pathway .

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gαq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors, and identified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration in vitro. Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.