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.

Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent proteinuria and progressive decline in renal function, and is one of the microvascular complications of diabetes. With the in-depth understanding of the pathogenesis of DN, the role of intestinal flora imbalance in the disease has been found clinically. This suggests that restoring the host′s healthy gut flora may be a means of improving DN. In fact, recent studies have shown that many of the drugs currently used to treat DN affect gut microbiota composition. In this review, intestinal flora is regarded as one of the main factors affecting the development of DN, and DN therapy targeting intestinal flora is summarized to provide new ideas for the diagnosis and treatment of DN.

Objective To describe the status and influencing factors of psychological distress in older people living with HIV in Shanghai.Methods Convenience sampling was used to select HIV patients with the age of 50 years old and above who attended follow-up visits at the voluntary counselling & testing clinic in Shanghai Public Health Clinical Center from December 2022 to October 2023.Data were collected using a general information questionnaire,HIV disclosure questionnaire,Distress Thermometer and Lubben Social Network Scale-6.Binary logistic regression was employed to analyze the factors influencing psychological distress.Results The prevalence of psychological distress among 332 participants was 105 cases(31.6％).The top 3 items selected by participants in Psychological Distress Problem List were insurance/financial issues,worry and sleep,relationship with children.Factors associated with a higher level of psychological distress included lower monthly income,not HIV disclosure and higher levels of social isolation.Conclusion Psychological distress among older people living with HIV remains to be further reduced,and it is affected by many factors.Health care providers should pay more attention to psychological distress among older HIV patients,and develop targeted intervention according to relevant influencing factors,aiming to reduce their psychological distress.