Background: One of the major concerns in cancer treatment and clinical translation of many anti-cancer compounds has been their potential toxicities, especially hepatotoxicity. Nanoparticle (NP) holds great potential to solve the problem, as many clinical studies have not shown increased hepatotoxicity for nanotherapeutics with higher accumulation in the liver. However, there are few studies investigating how nanoparticle assists in reducing hepatotoxicity. Herein, we demonstrated that nanoformulation of known hepatotoxic anti-cancer compounds showed lower hepatotoxicity than their small molecule counterparts. Importantly, we demonstrated that slower drug release is associated with reduced hepatotoxicity. We also showed that that Kupffer cell uptake in the liver reduce nanotherapeutics’ hepatotoxicity. Methods: Two different antineoplastic drugs with high hepatotoxicity, SN-38 and wortmannin (Wtmn), were encapsulated into lipid shell-PLGA core nanoparticles separately. NP release kinetics were controlled by adjusting lipids/polymer ratio for fast (Fast-NPs), medium (Medium-NPs) and slow drug release profile (Slow-NPs), respectively. Hepatotoxicity of NPs or free drugs was analyzed by assessing serum ALT and AST levels post intravenous injection at ½ MTD in CD-1 mice. IHC staining of HO-1 and Mn-SOD was also used to show liver damage. In vitro hepatotoxicity of primary hepatocytes after Kupffer cell uptake was assessed by MTS assay and LDH assay. In vivo macrophage depletion was achieved using clodrosome. Results: Nanoformulations of SN-38 and Wtmn showed lower ALT and AST levels than their small molecule counterparts 12 h and 24 h post treatment. The liver damage was further confirmed with IHC staining of Mn-SOD and HO-1. To address the effect of drug release kinetics on hepatotoxicity, we showed that over 90% of drugs were released within 24 h in Fast-NP. While the release rate of Slow-NPs was 66.8% for SN-38 and 67.5% for Wtmn. We showed that Slow-NPs of Wtmn resulted in minimal increase of ALT and AST levels. Compared to the baseline in untreated mice, the ALT level was 2.3-fold for Slow-NPs, 4.4-fold for Medium-NPs and 6-fold for fast-NPs; meanwhile, the AST level was 1.6-fold, 2.5-fold and 3.6-fold, respectively. To assess the effect of Kupffer cell uptake in hepatotoxicity, we found that the toxicity of the nanotherapeutics for primary hepatocytes significantly reduced after Kupffer cell uptake in vitro. We further confirmed it in vivo by depleting Kupffer cells in CD-1 mice. We demonstrated that ALT and AST levels of nanotherapeutics significantly increased to the levels comparable to free drugs after Kupffer cell depletion. Conclusions: We demonstrate that nanoparticle reduces hepatotoxicity of cancer treatment by controlled release and Kupffer cell uptake. Our work bridges an important knowledge in nanoparticle drug delivery and clinical translation of nanomedicine. Citation Format: Yu Mi, Feifei Yang, Andrew Z. Wang. Nanoparticle reduces hepatotoxicity of cancer treatment by controlled release and Kupffer cell uptake [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3899.

Background Maintenance hemodialysis (MHD) patients have complex medication regimens that require a high level of skill to interpret medication information. However, there is currently a lack of research evaluating the ability to read and understand medication labels in Chinese MHD patients. In addition, the relationship between frailty and medication literacy among MHD patients remains unclear. Therefore, this study aims to assess the potential factors affecting medication literacy in MHD patients and to explore the relationship between frailty and medication literacy. Methods This cross-sectional study was conducted using convenience sampling in West China Hospital of Sichuan University, China. Using a general questionnaire, we collected demographic, clinical and laboratory data. Medication literacy was assessed by the Chinese Medication Literacy Scale, and frailty was assessed by the FRAIL Scale. Univariate analyses examined potential factors impacting medication literacy. An ordered logistic regression was used to analyze the relationships between medication literacy and these factors. Spearman's correlation was used to assess the association between medication literacy and frailty. Results A total of 290 MHD patients were included in the analysis. Inadequate, marginal, and adequate medication literacy was found in 56 (19.3%), 153 (52.8%), and 81 (27.9%) patients, respectively. Ordered logistic regression revealed factors impacting medication literacy: age (OR = 3.561, 95% CI = 1.769–7.171, p < 0.001 for < 65 years); education (OR = 0.116, 95% CI = 0.048–0.284, p < 0.001 for ≤ primary school education; OR = 0.294, 95% CI = 0.145–0.594, p = 0.001 for junior high school education); caregiver medication assistance (OR = 0.434, 95% CI = 0.221–0.852, p = 0.015); frailty (OR = 2.275, 95% CI = 1.120–4.621, p = 0.023 for prefrail patients); and β2-microglobulin (β2-MG) (OR = 0.990, 95% CI = 0.982–0.998, p = 0.012). Spearman's analysis showed that medication literacy was associated with frailty in MHD patients (R=-0.189, p = 0.001). Conclusions The Chinese version of the MedLitRxSE tool can help evaluate medication literacy in MHD patients. Medication literacy levels in MHD patients need improvement and differ among patient groups, such as by age, education, caregiver support, β2-microglobulin levels, and risk of frailty.

Background: Mycoplasma genitalium (MG) causes urogenital tract infections and is associated with reproductive morbidity. Although MG has been reported across many regions and population groups, it is not yet routinely tested for in China. Our study contributes to current research by reporting the prevalence and correlates of MG infection in patients attending a sexually transmitted infection (STI) clinic in Guangdong from Jan 2017-May 2018.Methods: Urethral (from 489 men) and endo-cervical (from 189 women) samples, blood samples, and patient histories (via questionnaires) were collected. Doctors clinically diagnosed anogenital warts (GW) during the examination (n=678). The presence of MG was evaluated using an in-house via polymerase chain reaction protocol. We also tested all participants for herpes simplex virus-2 (HSV-2), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV. Univariate and multivariate logistic regression were used to evaluate factors associated with MG.Results: MG was detected in 7.2% (49/678) of the patients (men, 7.4%; women, 6.9%). The MG positivity rate was 14.2% among symptomatic patients, and 5.6% for asymptomatic patients , respectively. Only 36.7% (18/49) Mg positive patients were symptomatic. Among the MG-infected patients, 10.2% were co-infected with CT, 6.1% with NG, 8.2% with HSV-2, 4.1% with syphilis and 22.4% with GW. Presentation with clinical symptoms was significantly associated with MG infection [OR=2.52 (2.03-3.13)]. In our analysis, MG was not associated with other STIs.Conclusions: MG is a relatively common infection among individuals attending an STI clinic in Guangdong Province. Routine testing of symptomatic patients may be necessary, and more epidemiological studies are needed to provide evidence for future testing guidelines,

Background Mycoplasma genitalium (MG) is known to cause urogenital tract infections and is associated with reproductive morbidity. Although MG has been reported across many regions and population groups, it is not yet routinely tested for in China. Our study contributes to current research by reporting the prevalence and correlates of MG for patients attending a sexually transmitted infection (STI) clinic in Guangdong from Jan 2017-May 2018.Methods Urethral (489 men) and endo-cervical (189 women) samples, blood samples, and patient histories (via questionnaires) were collected. Doctors clinically diagnosed anogenital warts (GW) during the examination (n=678). Presence of MG was tested using an in-house polymerase chain reaction. We also tested all participants for herpes simplex virus-2 (HSV-2), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV. Univariate and multivariable logistic regressions were used to evaluate factors associated with MG.Results MG was detected among 7.2% (n=49) of patients (7.4% men, 6.9% women). Of 629 heterosexual patients, the MG was detected in 7.5% (47/629), and of 49 MSM, MG was detected in 4.1% (2/49). Among MG-infected patients, 10.2% were co-infected with CT, 6.1% with NG, 8.2% with HSV-2, 4.1% with syphilis and 22.4% with GW. Among 152 symptomatic patients, the prevalence of MG was 12.5% (n=19, of whom 17 were men). Being symptomatic was statistically significant for MG infection [OR=2.2(1.3~3.8)].Conclusion MG is a relatively common infection among individuals attending an STI clinic in Guangdong province. To make MG testing available and routinely screen symptomatic patients with urinary and /or cervical discharge in STI clinics in China is essential.