[An exploratory clinical study of the efficacy and safety of tumor-infiltrating lymphocytes in the treatment of metastatic osteosarcoma].

Objective: To explore the safety and efficacy of tumor-infiltrating lymphocytes (TILs) extracted from tumor tissue in patients with pulmonary metastasis of osteosarcoma, the TILs were amplified in vitro to reach clinical dosage and reinfused to the patients combined with high-dose interleukin 2 (IL-2). Methods: Twelve subjects with pathologically diagnosed osteosarcoma were enrolled from December 2019 to June 20, 2021 in Shanghai General Hospital. All subjects progressed with metastasis after standard chemotherapy and failed multiple lines of treatments. Fresh tumor tissue was obtained from the metastatic site and extracted and amplified by Good Manufacturing Practice (GMP) workshop to produce TILs to clinical treatment dosage (109-1011). High-dose IL-2 (100 000-200 000 U/kg) was administered immediately after autogenous TILs infusion to promote the activation, proliferation and antitumor cytolytic activity in vivo. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) standard and tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results: One patient did not receive treatment due to failure in isolating TILs, total of 11 patients received a single re-infusion of autologous TILs. There were 10 males and 1 female with a median age of 19.9 years (12-33 years). Six of these patients received higher dose levels of 1.0×1010 TILs. The 11 patients were followed-up for 1 to 13 months and tolerated well. The most common adverse events reported were fever (10/11), constipation (3/11) and elevated gamma-glutamyl transferase (GGT) (3/11). The high incidence of fever was due to the IL-2 infusion. All patients experienced a transient drop in lymphocyte count and leukopenia leading to non-myeloid ablative lymphocyte clearance. The AE included grade 4 hematologic toxicity, including 8 cases of lymphocytopenia, 2 cases of neutropenia and 1 case of thrombocytopenia. No AE of neurotoxicity occurred. Of all the 11 patients, 9 patients got stable disease (SD) and 2 patients had progressive disease (PD). The disease control rate was 9/11. The median duration of SD was more than 4 months, and the maximum tumor volume decreased by close to 20%. Patient number 9 had sustained SD status for more than 6 months. Conclusions: TILs with in vitro expansion ability could be isolated from tumor tissues of advanced osteosarcoma patients. TILs amplified and reinfused in vitro have anti-osteosarcoma activity.

Ligustilide, a major bioactive component of Angelica sinensis, promotes bone formation via the GPR30/EGFR pathway.

Angelica sinensis (Oliv.) Diels is a widely-used traditional Chinese herbal medicine in treating osteoporosis. Ligustilide (LIG) is the main component of A. sinensis and is considered to be the most effective biologically active ingredient in this plant. LIG has been found to have multiple pharmacological activities, such as anti-atherosclerosis, neuroprotection, anticancer, anti-inflammatory and analgesic. However, little is known regarding its anti-osteoporotic effects. The aims of this study were to investigate any protective effect of LIG on bone formation. The results showed that LIG significantly ameliorated inhibition of bone formation in zebrafish caused by prednisolone. LIG promoted osteoblast differentiation, including that of the pre-osteoblastic cell line MC3T3-E1 and bone marrow mesenchymal stem cells. LIG greatly improved the viability of MC3T3-E1 cells exposed to H2O2, attenuated H2O2-induced apoptosis and increased the expression of Bcl-2. Furthermore, LIG treatment lead to marked activation of phosphorylated EGFR and ERK1/2. These effects could be obviously inhibited by blocking GPR30 signaling with the specific inhibitor G15. Collectively, the results reveal that GPR30 is a positive switch for LIG to increase bone formation via regulation of EGFR, and these results provide evidence for the potential of LIG to treat osteoporosis.

[Diagnostic value of contrast-enhanced CT scans in identifying lung adenocarcinomas manifesting as ground glass nodules].

Objective: To investigate the value of contrast-enhanced CT scans in differential diagnosis of atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimal invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) in patients who manifested as ground glass nodules (GGNs) or mixed GGNs (mGGNs) in unenhanced CT imaging. Methods: The unenhanced and enhanced CT images of 194 patients with GGNs in the lung were retrospectively analyzed, including 64 cases with pre-invasive lesions, 80 cases with MIA, and 50 cases with IAC. The prediction of pathological types was based on maximal diameters and the solid portions of the lesions displayed on unenhanced and enhanced CT images, and then compared with pathological diagnosis. Results: In 64 patients with pre-invasive lesions, the CT value increased in 59 cases after contrast-enhanced administration, whereas the solid portions increased in 5 cases. In the 80 patients with MIA, solid portions increased in 50 cases and the CT value increased in 30 cases after contrast administration. In 50 cases with IAC, almost all of them showed increased solid portions, whereas only 2 cases showed an increase of CT values. In the pre-invasive group and the MIA group, the increase of CT values after contrast administration was (45.88±15.97) HU and (66.47±44.54) HU, respectively, showing statistically significant difference (P=0.001). The increase of solid portions in the MIA group and IAC group was (1.55±0.73) mm and (1.88±0.75) mm, respectively, also showing significant difference (P=0.032). Conclusion: Contrast-enhanced CT scans were more useful than unenhanced CT scans for the diagnosis of lung adenocarcinomas manifesting as GGNs .

CT features differentiating pre- and minimally invasive from invasive adenocarcinoma appearing as mixed ground-glass nodules: mass is a potential imaging biomarker.

AIM: To investigate the differential diagnosis value of preoperative computed tomography (CT) features between pre/minimally invasive and invasive adenocarcinoma in pulmonary mixed ground glass nodules (mGGNs). MATERIALS AND METHODS: The histopathological data and CT images of 146 mGGNs in 141 patients were reviewed retrospectively. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to identify the CT features differentiating between pre/minimally invasive and invasive adenocarcinoma and to evaluate their accuracy. RESULTS: In univariate analysis, there were significant differences (p<0.05) in the nodule diameter, volume, density, mass, solid portion volume, shape, margin, air bronchogram, and pleural retraction between pre/minimally invasive and invasive adenocarcinoma. Multivariate logistic regression analyses revealed that nodule mass and volume were statistically significant independent differentiators. ROC curve analysis was performed to evaluate the differentiators. According to the corresponding ROC curve, the optimal cut-off mass to differentiate pre/minimally invasive adenocarcinoma from invasive adenocarcinoma was 254.87 mg, with a sensitivity of 84.52%, a specificity of 88.71%, and an accuracy of 86.30%. Compared with the area under the ROC curve (AUC) for mass, volume, and diameter, the differential diagnosis value of mass was higher than those of volume and diameter. CONCLUSION: Nodule mass and volume were significant differentiators of pre/minimally invasive adenocarcinoma from invasive adenocarcinoma in mGGN, and mass had a higher differential diagnosis value.

[Effect of rapamycin and chloroquine on osteosarcoma].

Objective: To investigate the combination effect of anti-tumor agent rapamycin and anti-autophagy agent chloroquine on osteosarcoma. Methods: The inhibition effect of rapamycin or chloroquine and combination of both on human osteosarcoma cell line 143B measured with CCK-8 box.The combination index at different concentration was calculated, and the synergism effect range was analysed.The effect of combined therapy on cell cycle and apoptosis via flow cytometric was analyzted.Setting up murine subcutaneous xenograft model, the combination effect of antitumor in vivo observed. Results: Either of them, rapamycin or chloroquine had an antitumor effect in vitro (RAPA: IC50=1.5 nmol/L; CQ: IC50=400 µmol/L). When the inhibition rate 40%

A comparison of regional and general anaesthesia for total replacement of the hip or knee: a meta-analysis.

We performed a meta-analysis to evaluate the relative efficacy of regional and general anaesthesia in patients undergoing total hip or knee replacement. A comprehensive search for relevant studies was performed in PubMed (1966 to April 2008), EMBASE (1969 to April 2008) and the Cochrane Library. Only randomised studies comparing regional and general anaesthesia for total hip or knee replacement were included. We identified 21 independent, randomised clinical trials. A random-effects model was used to calculate all effect sizes. Pooled results from these trials showed that regional anaesthesia reduces the operating time (odds ratio (OR) -0.19; 95% confidence interval (CI) -0.33 to -0.05), the need for transfusion (OR 0.45; 95% CI 0.22 to 0.94) and the incidence of thromboembolic disease (deep-vein thrombosis OR 0.45, 95% CI 0.24 to 0.84; pulmonary embolism OR 0.46, 95% CI 0.29 to 0.80). Regional anaesthesia therefore seems to improve the outcome of patients undergoing total hip or knee replacement.

Danggui-Shaoyao-San, a traditional Chinese prescription, suppresses PGF2alpha production in endometrial epithelial cells by inhibiting COX-2 expression and activity.

Danggui-Shaoyao-San, a famous traditional Chinese prescription, has been widely used in China for treating various gynecological inflammatory diseases including dysmenorrhea, but it is still poorly understood how it works on those inflammatory disorders. Prostaglandin F(2alpha) (PGF(2alpha)), one important mediators of inflammation, plays crucial roles in the pathological mechanism responsible for dysmenorrhea. Here, we demonstrate that Danggui-Shaoyao-San significantly suppresses oxytocin-evoked PGF(2alpha) production of rat endometrial epithelial cells in a concentration-dependent manner. Furthermore, Danggui-Shaoyao-San-mediated down-regulation of cyclooxygenases-2 message RNA transcription, protein expression and enzyme activity in endometrial epithelial cells may be involved in the inhibitory effect on PGF(2alpha) production. Our study provides a possible mechanism for the bioactivity of Danggui-Shaoyao-San for treating dysmenorrhea and other gynecological disorders.