[A nomogram for predicting residual back pain after percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

OBJECTIVE: To construct percutaneous vertebroplasty for predicting osteoporotic vertebral compression fractures (OVCFs) nomogram of residual back pain (RBP) after percutaneous vertebroplasty(PVP). METHODS: Clinical data of 245 OVCFs patients who were performed PVP from January 2020 to December 2022 were retrospectively analyzed, including 47 males and 198 females, aged from 65 to 77 years old with an average of (71.47±9.03) years old, and were divided into RBP group and non-RBP group according to whether RBP occurred. Gender, age, comorbidities, fracture stage, body mass index (BMI), bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI) and other general information were collected; anterior vertebral height (AVH), anterior vertebral height ratio (AVH), anterior vertebral height ratio(AVHR), Cobb angle, intravertebral vacuum cleft (IVC), thoracolumbar fascia (TLF) injury, paravertebral muscle steatosis, injection volume and leakage of bone cement, bone cement dispersion pattern, anterior vertebral height recovery ratio (AVHRR), Cobb angle changes, etc. imaging parameters before operation and 24 h after operation were collected. Univariate analysis was performed to analysis above factors, and multivariate Logistic regression model was used to investigate independent risk factors for postoperative RBP, and Nomogram model was constructed and verified;receiver operating characteristic(ROC) curve and calibration curve were used to determine predictive performance and accuracy of the model, and Hosmer-Lemeshow (H-L) test was used for evaluation. The area under curve (AUC) of ROC was calculated, and Harrell consistency index (C index) was used to evaluate the predictive efficiency of model;decision curve analysis (DCA) was used to evaluate clinical practicability of model. RESULTS: There were 34 patients in RBP group and 211 patients in non-RBP group. There were no significant differences in gender, age, comorbidities, fracture stage, BMI, BMD, VAS, ODI, AVH, AVHR and Cobb angle between two groups (P>0.05). Univariate analysis showed 6 patients occurred IVC in RBP group and 13 patients in non-RBP, the number of IVC in RBP group was higher than that in non-RBP group (χ2=5.400, P=0.020);6 patients occuured TLF injury in RBP group and 11 patients in non-RBP group, the number of TLF injury in RBP group was higher than that in non-RBP group (χ2=7.011, P=0.008);In RBP group, 18 patients with grade 3 to 4 paraptebral steatosis and 41 patients in non-RBP group, RBP group was higher than non-RBP group (χ2=21.618, P<0.001), and the proportion of bone cement mass in RBP group was higher than non-RBP group (χ2=6.836, P=0.009). Multivariate Logistic regression analysis showed IVC (χ2=4.974, P=0.025), TLF injury (χ2=5.231, P=0.023), Goutallier grade of paravertebral steatosis >2 (χ2=15.124, P<0.001) and proportion of bone cement (χ2=4.168, P=0.038) were independent risk factors for RBP after PVP. ROC curve of model showed AUC of original model was 0.816[OR=2.862, 95%CI (0.776, 0.894), P<0.001]. The internal verification of model through 200 bootstrap samples showed the value of C index was 0.936, and calibration curve showed predicted probability curve was close to actual probability curve. H-L goodness of fit test results were χ2=5.796, P=0.670. DCA analysis results showed the decision curve was above None line and All line when the threshold value ranged from 6% to 71%. CONCLUSION: IVC, TLF combined injury, paravertebral muscle steatosis with Goutallier grade> 2, and bone cement diffusion with mass type are independent risk factors for RBP after PVP. The risk prediction model for RBP after PVP established has good predictive performance and good clinical practicability.

Upregulation of PIK3IP1 monitors the anti-cancer activity of PI3Kα inhibitors in gastric cancer cells.

Gastric cancer remains one of the most malignant cancers in the world. The target-based drugs approved by FDA for gastric cancer treatment include only three targets and benefit a small portion of gastric cancer patients. PIK3CA, a confirmed oncogene, mutates in 7-25% gastric cancer patients. PI3Kα inhibitor BYL719 has been approved for treating specific breast cancer. However, there is no comprehensive study about PI3Kα inhibitor in gastric cancer. In this study, we found pharmacological inhibition or knockdown of PI3Kα effectively inhibited the proliferation of partial gastric cancer cells. Then, we systematically explored the potential biomarkers for predicting or monitoring treatment response according to previous reports and found that basal expression of several receptor tyrosine kinases were related with the sensitivity of gastric cancer cells to BYL719. Next, RNA-seq technique was utilized and showed that BYL719 inhibited Myc targets V2 gene set in sensitive gastric cancer cells, and western blotting further verified that c-Myc was only inhibited in sensitive gastric cancer cells. More importantly, we firstly found BYL719 significantly elevated the expression of PIK3IP1 in sensitive gastric cancer cells, which was also observed in NCI-N87 cell derived xenograft mice models. Meanwhile, knockdown of PIK3IP1 partially rescued the cell growth inhibited by BYL719 in sensitive gastric cancer cells, suggesting the important role of PIK3IP1 in the antitumor activity of BYL719. In conclusion, our study provides biological evidence that PI3Kα is a promising target in specific gastric cancer and the elevation of PIK3IP1 could supply as a biomarker that monitoring treatment response.

Discovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway.

Mitochondria are known as "powerhouse of cells" and play the role of a bridge in redox balance, cell apoptosis, and autophagy. ROS accumulation can cause mitochondria damage, while the injured mitochondria will further enhance ROS levels reciprocally. Herein, we synthesized a novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compounds 4a-4v and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds 4o and 4p inhibited gastric cancer cells at micromolar level. Compound 4o caused G2/M arrest and induced mitochondria-dependent apoptosis in MGC-803 and SGC-7901. However, inhibiting apoptosis pathway cannot prevent the inhibitory activity of compound 4o against gastric cancer cell. To our surprising, ROS level was increased by compound 4o and elevation of ROS could be rescued by NAC. In accordance with that, NAC absolutely prevented the anti-proliferation efficacy of compound 4o. We further found that autophagy inhibitor CQ rather than 3-MA partially reversed inhibitory activity of compound 4o in MGC-803 cells. Taken together, compound 4o exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound 4o may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.