Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective:To explore the therapeutic effect of group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Methods:This study used a randomized controlled trial design to compare GCBT with routine medication treatment. Unmedicated ninety-four patients who met the inclusion criteria were recruited and randomly allocated to GCBT group ( n=47) and drug treatment group ( n=47) by a simple random grouping method using the RAND function in Excel software which generated a table of random numbers to form a random grouping sequence. Both groups were treated for 12 weeks. The average reduction rate and value of Y-BOCS, HAMA 14 and HAMD 24 were compared between the two groups, t-test,chi-square (χ 2) test and variance analysis (ANOVA) were condulted to analyze data. Results:(1) There was no significant difference between two groups in Y-BOCS and HAMA 14 scores at baseline ( t=0.281, P=0.779; t=0.795, P=0.429), but HAMD 24 scores were significantly different ( t=2.316, P<0.05). Sixteen patients in GCBT group and sixteen in drug treatment group dropped out of treatment, resulted a total drop-out rate of 34%. There was no significant difference in the drop-out rate between the two groups. (2) After 12-week treatment, the Y-BOCS scores decreased compared to pre-treatment in both groups. There was no statistical difference in the mean reduction rate ((37.0±27.4)% vs. (45.5±22.9)%) and score (9.0±6.3 vs.11.0±5.8) of Y-BOCS ( F(1,62)=0.069, P=0.794; F(1,62)=0.001, P=0.975) before and after treatment between the two groups. There was no statistical difference in the effective and cure rate between the two groups (χ 2=1.653, P=0.199; χ 2=0.088, P=0.767) . (3) There was no significant difference in the mean reduction rate and score of HAMA 14 ( t=-0.922, P=0.362; t=1.082, P=0.286). (4) No significant difference was found regarding the mean reduction rate of HAMD 24 between the two groups, but the mean reduction scores of HAMD 24 in the medication group were significantly higher than those in GCBT group ( t=2.239, P=0.029). Conclusion:GCBT is equivalent to conventional medication treatment for obsessive-compulsive and anxiety symptoms for OCD patients, and medication treatment is superior to GCBT in depressive symptoms.

Objective:To explore the therapeutic effect of group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Methods:This study used a randomized controlled trial design to compare GCBT with routine medication treatment. Unmedicated ninety-four patients who met the inclusion criteria were recruited and randomly allocated to GCBT group ( n=47) and drug treatment group ( n=47) by a simple random grouping method using the RAND function in Excel software which generated a table of random numbers to form a random grouping sequence. Both groups were treated for 12 weeks. The average reduction rate and value of Y-BOCS, HAMA 14 and HAMD 24 were compared between the two groups, t-test,chi-square (χ 2) test and variance analysis (ANOVA) were condulted to analyze data. Results:(1) There was no significant difference between two groups in Y-BOCS and HAMA 14 scores at baseline ( t=0.281, P=0.779; t=0.795, P=0.429), but HAMD 24 scores were significantly different ( t=2.316, P<0.05). Sixteen patients in GCBT group and sixteen in drug treatment group dropped out of treatment, resulted a total drop-out rate of 34%. There was no significant difference in the drop-out rate between the two groups. (2) After 12-week treatment, the Y-BOCS scores decreased compared to pre-treatment in both groups. There was no statistical difference in the mean reduction rate ((37.0±27.4)% vs. (45.5±22.9)%) and score (9.0±6.3 vs.11.0±5.8) of Y-BOCS ( F(1,62)=0.069, P=0.794; F(1,62)=0.001, P=0.975) before and after treatment between the two groups. There was no statistical difference in the effective and cure rate between the two groups (χ 2=1.653, P=0.199; χ 2=0.088, P=0.767) . (3) There was no significant difference in the mean reduction rate and score of HAMA 14 ( t=-0.922, P=0.362; t=1.082, P=0.286). (4) No significant difference was found regarding the mean reduction rate of HAMD 24 between the two groups, but the mean reduction scores of HAMD 24 in the medication group were significantly higher than those in GCBT group ( t=2.239, P=0.029). Conclusion:GCBT is equivalent to conventional medication treatment for obsessive-compulsive and anxiety symptoms for OCD patients, and medication treatment is superior to GCBT in depressive symptoms.