Objective:To evaluate the effect and safety of rifabutin combined with multi-drugs in the treatment of multi-drug resist-ant tuberculosis with long-term therapy. Methods:Totally 86 cases of patients with multi-drug resistant tuberculosis were divided into the control group and the treatment group with 43 ones in each according to a random number table method. The two groups were trea-ted with levofloxacin, pasiniazid, ethambutol, protionamide and amikacin etc. The control group was treated with rifapentine, and the treatment group was treated with rifabutin additionally. After 18-month treatment, the negative conversion ratio of sputum smear and sputum mycobacterium tuberculosis culture, lesion absorption rate and cavity closure rate of X-ray chest radiograph and adverse reac-tions in the two groups were compared. Results:The negative conversion ratio of sputum smear and sputum mycobacterium tuberculosis culture in the treatment group was 41. 86% and 32. 56%, respectively, which were similar with those in the control group ( P >0. 05). There were no significant differences in lesion absorption rate and cavity closure rate of X-ray chest radiograph and adverse re-actions between the two groups (P>0. 05). Conclusion:Rifapentine or rifabutin combined with multi-drugs in the treatment of multi-drug resistant tuberculosis can improve the negative conversion rate of sputum mycobacterium and lesion absorption and cavity closure with high safety.

BACKGROUNDBrachytherapy offers an innovative method of delivering conformal high-dose radiation to a defining target tumor. The aim of this study is to investigate the value and effect of using radioactivity ¹²⁵I seed permanent implants combined with chemotherapy in the management of stage III or IV lung cancer.

METHODSForty-two lung cancer patients in stage III and IV (15 center lung cancer) who couldn't be relieved by routine methods were treated with ¹²⁵I seed permanent micropuncture implant brachytherapy and chemotherapy. The dose and distribution of seeds was decided by treatment planning system, and CT was used during ¹²⁵I seed permanent implant treatment. Distribution of seeds and complication was reviewed by CT scan after treatment. Chemotherapy was performed in 3 to 7 days after implanting. The effect was observed by X-ray, CT and MRI every 3 or 4 weeks.

RESULTSThe satisfaction rate of seed distribution was 83.3% (35/42). The response rate of treatment was 85.7% (36/42), including complete response rate 26.2% (11/42), partial response rate 59.5% (25/42), no change rate 14.3% (6/42). Effective rate of pain relief was 83.3% (15/18). Thirteen patients (31.0%) had complication of mild hemothorax, 8 (19.0%) with bleeding in lung and 5 (11.9%) with hemoptysis. Three patients (7.1%) had mild pneumothorax and 1 patient (2.4%) had a malposition seed. Leucopenia and radiation pneumonia didn't occurred.

CONCLUSIONS¹²⁵I seed micropuncture implant has less trauma and complication, and is a safe and effective method. This method might be helpful in the treatment of lung cancer and can be selectively used in clinic.

Objective:To investigate the safety and dose of 4D template (real-time adjustable angle template) in the treatment of advanced malignant tumors with 125I seeds. Methods:98 patients with advanced malignant tumors admitted to Department of Thoracic Surgery of Shaanxi Provincial Tumor Hospital were treated with 4D template-navigated radioactive 125I seed implantation from June 2018 to December 2019. Preoperative TPS plan, intraoperative optimization, postoperative verification of immediate dose and postoperative evaluation of implantation dose were performed. The treatment results were observed. Results:All 98 patients completed the seed implantation. The implantation dose of GTV of implantation site receiving external irradiation was (12 489±414) cGy and the dose of no external irradiation was (15 036±514) cGy. V 100% was 84.7%-94.1%, and 88.2%-93.7%. The implantation dose of CTV was (7 450±621) cGy, and (9 080±761) cGy. The quality of dose implantation was evaluated as: excellent in 89 cases (91%, 89/98), good in 7 cases (7%, 7/98), fair in 2 cases (2%, 2/98), and poor in 0 case, respectively. The symptom relief rate of patients with pain was 92%(36/39). The 1-and 2-year local control rates were 61%, 36% and 82%, 54% in patients treated with and without external irradiation, respectively. The difference was statistically significant ( P=0.02). The incidence rates of pneumothorax and hemoptysis were 19%(9/48) and 10%(5/48). No corresponding complications were observed in other parts of the patients. Conclusion:4D template-assisted 125I seed therapy is safe and effective for malignant tumors, and intraoperative adjustment of needle angle and dose optimization can realize the precise control of implantation dose.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.