A nomogram model of spectral CT quantitative parameters and clinical characteristics predicting lymphovascular invasion of gastric cancer.

Objective: The study established a nomogram based on quantitative parameters of spectral computed tomography (CT) and clinical characteristics, aiming to evaluate its predictive value for preoperative lymphovascular invasion (LVI) in gastric cancer (GC). Methods: From December 2019 to December 2021, 171 patients with pathologically confirmed GC were retrospectively collected with corresponding clinical data and spectral CT quantitative data. Patients were divided into LVI-positive and LVI-negative groups based on their pathological results. The univariate and multivariate logistic regression analyses were used to identify the risk factors and construct a nomogram. The calibration curve and receiver operating characteristic (ROC) curve were adopted to evaluate the predictive accuracy of nomogram. Results: Four clinical characteristics or spectral CT quantitative parameters, including Borrmann classification (P = 0.039), CA724 (P = 0.007), tumor thickness (P = 0.031), and iodine concentration in the venous phase (VIC) (P = 0.004) were identified as independent factors for LVI in GC patients. The nomogram was established based on the four factors, which had a potent predictive accuracy in the training, internal validation and external validation cohorts, with the area under the ROC curve (AUC) of 0.864 (95% CI, 0.798-0.930), 0.964 (95% CI, 0.903-1.000) and 0.877 (95% CI, 0.759-0.996), respectively. Conclusion: This study constructed a comprehensive nomogram consisting spectral CT quantitative parameters and clinical characteristics of GC, which exhibited a robust efficiency in predicting LVI in GC patients.

Effect of S-region mutations on HBsAg in HBsAg-negative HBV-infected patients.

BACKGROUND: Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. METHODS: Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. RESULTS: Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. CONCLUSIONS: HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.

ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway.

Osteoarthritis (OA) is the most common irreversible chronic joint dysfunction disease, which is pathologically characterized by disturbance of articular cartilage homeostasis leading to subsequent inflammatory response and cartilage extracellular matrix (ECM) degradation. Increasing evidence has demonstrated the dysregulation of transcription factors play crucial roles in the occurrence and development of osteoarthritis (OA), but the potential functions and mechanism of most transcription factors in OA has not been completely illuminated. In this study, we identified that transcription factor V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) was significantly down-regulated in OA cartilage and IL-1ß-induced OA chondrocytes. Functional experiments in vitro demonstrated that the overexpressed ETS2 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and ECM degradation in IL-1ß-induced OA chondrocytes, whereas the knockdown of ETS2 led to the opposite effects. Further in vivo studies have shown that up-regulated ETS2 dramatically ameliorates cartilage injury in DMM-induced OA mice. Mechanical studies have disclosed that DNMT1-mediated downregulation of ETS2 dramatically promotes STAT1 by inhibiting miR-155 transcription, and increased STAT1 initiates a feedback loop that may enhance DNMT1-mediated hypermethylation of ETS2 to inhibit ETS2 expression, thus forming a DNMT1/ETS2/miR-155/STAT1 feedback loop that inhibits MAPK signaling pathways and aggravates OA cartilage injury. In all, our results revealed that overexpression of ETS2 markedly ameliorated OA cartilage injury through the ETS2/miR-155/STAT1/DNMT1 feedback loop, providing a new perspective on the pathogenesis and therapeutic strategies for OA.

Alisertib exerts KRAS allele­specific anticancer effects on colorectal cancer cell lines.

The aim of the present study was to examine the effects of alisertib (ALS) on RAS signaling pathways against a panel of colorectal cancer (CRC) cell lines and engineered Flp-In stable cell lines expressing different Kirsten rat sarcoma virus (KRAS) mutants. The viability of Caco-2KRAS wild-type, Colo-678KRAS G12D, SK-CO-1KRAS G12V, HCT116KRAS G13D, CCCL-18KRAS A146T and HT29BRAF V600E cells was examined by Cell Titer-Glo assay, and that of stable cell lines was monitored by IncuCyte. The expression levels of phosphorylated (p-)Akt and p-Erk as RAS signal outputs were measured by western blotting. The results suggested that ALS exhibited different inhibitory effects on cell viability and different regulatory effects on guanosine triphosphate (GTP)-bound RAS in CRC cell lines. ALS also exhibited various regulatory effects on the PI3K/Akt and mitogen-activated protein kinase (MAPK) pathways, the two dominant RAS signaling pathways, and induced apoptosis and autophagy in a RAS allele-specific manner. Combined treatment with ALS and selumetinib enhanced the regulatory effects of ALS on apoptosis and autophagy in CRC cell lines in a RAS allele-specific manner. Notably, combined treatment exhibited a synergistic inhibitory effect on cell proliferation in Flp-In stable cell lines. The results of the present study suggested that ALS differentially regulates RAS signaling pathways. The combined approach of ALS and a MEK inhibitor may represent a new therapeutic strategy for precision therapy for CRC in a KRAS allele-specific manner; however, this effect requires further study in vivo.

Practical nomogram based on comprehensive CT texture analysis to preoperatively predict peritoneal occult metastasis of gastric cancer patients.

Objectives: This study aims to evaluate whether a nomogram based on comprehensive CT texture analysis of primary tumor and peritoneotome combined with conventional CT signs can preoperatively predict peritoneal occult metastasis in gastric cancer patients. Methods: A total of 1,251 patients with gastric cancer (GC) were retrospectively analyzed in Fujian Province Hospital between 2008 and 2020. Patients from the occult peritoneal metastasis (PM) group were initially diagnosed as PM-negative on CT and later confirmed as PM-positive through laparoscopy or surgery. The group without PM was randomly sampled from patients without PM. The preoperative CT signs and texture features and clinical characteristics of patients were retrospectively analyzed. Hazard factors of occult PM were identified by univariate analysis and multivariate logistic regression analysis, which were intended for creating prediction models. A nomogram was established based on the model with the highest predictive efficacy and clinical application value. Results: A total of 31 patients with occult PM and 165 patients without PM were enrolled in this study. The maximum size, thickness, enhancement, serous involvement of primary GC tumor and ascites on CT, and texture features such as inhomogeneity of the primary tumor, standard deviation, and inhomogeneity of the peritoneum were determined as independent predictors that could be jointly applied to predict occult PM. We separately constructed five forecast models using CT signs, primary tumor texture, peritoneum texture, primary tumor texture + peritoneum texture, and their combination for predicting occult PM. These five prediction models achieved an AUC value of 0.832, 0.70, 0.784, 0.838, and 0.941, respectively. The DeLong test and Decision Curve Analysis (DCA) showed that the joint model, containing three meaningful CT signs (maximum size, thickness, and ascites) and two meaningful texture parameters (inhomogeneity of the primary tumor and inhomogeneity of the peritoneum), possessed the best predictive performance and clinical application (p<0.05). A forecast nomogram was subsequently established from the model above-mentioned. The calibration curves of the nomogram indicated a good consistency (a concordance index of 0.807) between the projection and the actual observation of occult PM. Conclusions: A practical projection nomogram based on the comprehensive CT texture analysis of a primary tumor and peritoneotome combined with conventional CT signs was constructed in our study, which can be conveniently used in preoperative personalized prediction of occult PM for GC patients, and acts as a recommendation for the optimization of clinical management.

Is traumatic meniscal lesion associated with acute fracture morphology changes of tibia plateau? A series of arthroscopic analysis of 67 patients.

BACKGROUND: Computed tomography (CT) has become a routine preoperative examination for tibial plateau fractures (TPFs). Assessing the location of the fragment and intercondylar eminence fracture can provide clinicians with valuable information; however, the evaluation of traumatic meniscal lesion (TML) and arthroscopic management are controversial. AIM: To predict TML by three-dimensional skeletal anatomy changes in unilateral TPF and bilateral TPF on preoperative thin layer CT. METHODS: Acute fracture of tibial plateau patients undergoing arthroscopic surgery between December 2017 and December 2019 were included in this retrospective study. The type, zone, and location of TMLs were diagnosed based on the operation records and/or arthroscopic videos. Measurement of three-dimensional fracture morphology included the following: Frontal fragment width of plateau, sagittal fragment subsiding distance (FSD), sagittal fracture line distance, sagittal posterior tibial slope, and transversal area ratio of fragment area) on preoperative CT three-dimensional plane. The correlation of TML with skeletal values was calculated according to unicondylar TPFs and bicondylar TPFs. RESULTS: A total of 67 patients were enrolled in this study, among which 30 patients had TMLs, lateral/medial (23/7). FSD was a particularly positive factor to predict TML, with odds ratio of 2.31 (1.26-5.63). On sagittal view of CT, FSD degree of 8 mm and posterior tibial slope exceeding 11.74° implied enhanced risk of TML in bicondylar TPFs. On coronal view, once fragment width of plateau surpassed 3 cm, incidence of TML reached 100%. On transverse view, area ratio of fragment as enhanced risk of 5.5% and FSD > 4.3 mm for predicting TML were observed in unicondylar TPFs. CONCLUSION: TML can be predicted by different parameters on preoperative CT views according to unicondylar fractures and bicondylar TPFs.

Icaritin, a novel plant-derived osteoinductive agent, enhances the osteogenic differentiation of human bone marrow- and human adipose tissue-derived mesenchymal stem cells.

For the treatment of diseases affecting bones using bone regenerative medicine, there is an urgent need to develop safe, inexpensive drugs that can strongly induce bone formation. In the present study, we systematically investigated the effects of icaritin, a metabolic product of icariin, on the osteogenic differentiation of human bone marrow­derived mesenchymal stem cells (hBMSCs) and human adipose tissue­derived stem cells (hADSCs) in vitro. After treatment with icaritin at concentrations of 10­8-10­5 M, hBMSCs and hADSCs were examined for alkaline phosphatase activity, osteocalcin (OC) secretion, matrix mineralization and expression levels of bone­related mRNA and proteins. Data showed that icaritin at concentrations 10­7-10­5 M significantly increased alkaline phosphatase activity, OC secretion at different time points, and calcium deposition at day 21. In addition, icaritin upregulated the mRNA expression of genes for bone morphogenetic proteins (BMP­2, ­4 and ­7), bone transcription factors (Runx2 and Dlx5) and bone matrix proteins (ALP, OC and Col­1). Moreover, icaritin increased the protein levels of BMPs, Runx2 and OC, as detected by western blot analysis. These findings suggest that icaritin enhances the osteogenic differentiation of hBMSCS and hADSCs. Icaritin exerts its potent osteogenic effect possibly by directly stimulating the production of BMPs. Although the osteogenic activity of icaritin in vitro was inferior to that of rhBMP­2, icaritin displayed better results than icariin. Moreover, the low cost, simple extraction procedure, and an abundance of icaritin make it appealing as a bone regenerative medicine.

[Comparative study on reconstruction of anterior cruciate ligaments with allografts and hamstring tendon under arthroscopy].

OBJECTIVE: To evaluate the effect of reconstruction of anterior cruciate ligaments (ACL) with allogeneic tendon or autologous hamstring tendon under arthroscopy. METHODS: Thirty-two cases of ACL injury (3 cases compound with PCL injury) were reviewed. All the patients were divided into two groups randomly. Fifteen cases were reconstructed with hamstring tendon, including 12 male and 3 female with the age ranging from 23 to 61 years. Seventeen cases were reconstructed with allograft, including 11 male and 6 female with the age ranging from 17 to 57 years. The tendons were fixed with absorbable or Ti screws. All patients were recorded symptoms,physical signs and Lysholm Scores two weeks after operation,and functional rehabilitation of knee six months after operation. RESULTS: All cases were followed up from 6 to 8 months. Pain and clinical symptoms disappeared and the function of knee joint was improved in all patients. Five patients of allograft with positive Lachman test result,one with severe graft rejection was found complete absorption of allograft under arthroscopy. No significant differences were seen in Lysholm Score between the two groups,average (88.5 +/- 7.2), (93.2 +/- 8.5) after operation (P > 0.05). CONCLUSION: The effects of reconstruction of cruciate ligaments with allogeneic tendon or autologous hamstring tendon under arthroscopy are more satisfying. But there are more symptoms and obvious individual differences in the earlier stage of rehabilitation. So reconstruction of cruciate ligaments under arthroscopy using autologous hamstring tendon should be performed as far as possible.

Effect of arsenic trioxide on human hepatocarcinoma in nude mice.

AIM: To study the effect of arsenic trioxide (As(2)0(3)) on human hepatoma cell line BEL-7402 in vivo. METHODS: Human hepatoma cell line BEL-7402 cultured in vitro was inoculated into nude mice and arsenic trioxide, 5-Fu and saline were injected into abdominal cavity of the nude mice respectively. The volumes of tumor and general conditions of the nude mice and structural changes of the liver and kidney were observed. Morphologic changes were studied under electron microscope. Expression of AFP was investigated by immunohistochemical method. RESULTS: As(2)O(3) could inhibit the growth of tumor. The tumor growth inhibitory rate in mice treated with 2.5 mg/kg As(2)O(3) was 53.42% on the tenth day. The tumor growth inhibitory rate in mice treated with 5 mg/kg As(2)O(3) was 79.28% on the fifth day and 96.58% on the tenth day respectively. As(2)O(3) did not damage the liver and kidney of nude mice, or affect the blood system. Typical apoptotic morphological changes were found under electron microscope, and the change of mitochondria was obvious. The expression rate of AFP declined after treatment. CONCLUSION: Arsenic trioxide can induce apoptosis of human hepatoma cells, and inhibit proliferation of tumor with no obvious side effects on liver and kidney.