The Association Between Household Financial Burden and Patient Mobility and Their Impact on Loss to Follow-Up Among Multidrug-Resistant Tuberculosis Patients in Guizhou, China.

Purpose: We aimed to assess the household financial burden due to multidrug-resistant tuberculosis (MDR-TB) treatment and its predictors, examine its association with patient mobility, and test their impact on patient loss to follow-up (LTFU). Methods: A cross-sectional study combining follow-up data collection was conducted at the largest designated MDR-TB hospital in Guizhou. Data were collected from medical records and questionnaires. Household financial burden was measured by the incidence of 2 indicators: catastrophic total costs (CTC) and catastrophic health expenditure (CHE). Mobility was classified as mover or non-mover after the patient's address was verified twice. A multivariate logistic regression model was used to identify associations between variables. Model I and Model II were separated by CHE and CTC. Results: Out of 180 households, the incidence of CHE and CTC was 51.7% and 80.6%, respectively. Families with low income and patients who were primary income earners were significantly associated with catastrophic costs. 42.8% of patients were movers. Patients from households with CHE (ORadj=2.2, 95% CI: 1.1-4.1) or with CTC (ORadj=2.6, 95% CI: 1.1-6.3) were more likely to move. Finding a job against financial difficulty (58.4%) was the top reason for movers. 20.0% of patients experienced LTFU. Patients from households with catastrophic payments (CHE: ORadj=4.1, 95% CI 1.6-10.5 in Model I; CTC: ORadj=4.8, 95% CI 1.0-22.9 in Model II), patients who were movers (ORadj=6.1, 95% CI 2.5-14.8 in Model I; ORadj=7.4, 95% CI 3.0-18.7 in Model II) and primary income earners (ORadj=2.5, 95% CI: 1.0-5.9 in Model I; ORadj=2.7, 95% CI 1.1-6.6 in Model II) had an increased risk of LTFU. Conclusion: There is a significant association between household financial burden due to MDR-TB treatment and patient mobility in Guizhou. They impact patients' treatment adherence and cause LTFU. Being a primary breadwinner increases the risk for catastrophic household payments and LTFU.

Hepatocyte ferroptosis contributes to anti-tuberculosis drug-induced liver injury: Involvement of the HIF-1α/SLC7A11/GPx4 axis.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common serious adverse event observed during the clinical treatment of tuberculosis. However, the molecular mechanisms underlying ATB-DILI remain unclear. A recent study has indicated that ferroptosis and lipid peroxidation may be involved in liver injury. Therefore, this study aimed to investigate the role of ferroptosis in the molecular mechanisms underlying ATB-DILI. Our results showed that anti-TB drugs induced hepatocyte damage in vivo and in vitro and inhibited BRL-3A cell activity in a dose-dependent manner, accompanied by increased lipid peroxidation and reduced antioxidant levels. Moreover, ACSL4 expression and Fe2+ concentration significantly increased following anti-TB drug treatment. Interestingly, anti-TB drug-induced hepatocyte damage was reversed by ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). In contrast, treatment with erastin (a ferroptosis inducer) resulted in further elevation of ferroptosis indicators. Additionally, we also found that anti-TB drug treatment inhibited HIF-1α/SLC7A11/GPx4 signaling in vivo and in vitro. Notably, HIF-1α knockdown significantly enhanced anti-TB drug-induced ferroptotic events and the subsequent exacerbation of hepatocyte damage. In conclusion, our findings indicated that ferroptosis plays a crucial role in the development of ATB-DILI. Furthermore, anti-TB drug-induced hepatocyte ferroptosis was shown to be regulated by HIF-1α/SLC7A11/GPx4 signaling. These findings shed new light on the mechanisms underlying ATB-DILI and suggest novel therapeutic strategies for this disease.

UXT, a novel DNMT3b-binding protein, promotes breast cancer progression via negatively modulating lncRNA MEG3/p53 axis.

Overexpressed ubiquitously expressed transcript (UXT) in breast tumors and derived cell lines modulated the transcriptional activity of estrogen receptor alpha. However, how UXT exerts its biological functions in the tumorigenicity of breast cancer remains largely unknown. Expressions of UXT and maternally expressed gene 3 (MEG3) were examined by qRT-PCR and Western blot. The capacity of cell proliferation, apoptosis, migration, and invasion was assessed using CCK-8, flow cytometry, and transwell assays. Methylation-specific PCR (MS-PCR) was employed to evaluate the methylation of the MEG3 imprinting control region. Co-immunoprecipitation was performed to verify the UXT/DNMT3b interaction. RNA immunoprecipitation (RIP) was subjected to assess the regulation of MEG3 on p53 activity. A xenograft tumor model was further conducted to certify the molecular mechanism. UXT was upregulated, while MEG3 was downregulated in breast cancer tissues and cell lines. UXT knockdown or MEG3 overexpression inhibited cell proliferation, promoted apoptosis, and weakened cell migration and invasion. Hypermethylation of the MEG3 imprinting control region was modulated by highly expressed DNMT3b. UXT inhibited MEG3 expression via recruiting DNMT3b to its imprinting control region. MEG3 positively regulated p53 activity. UXT negatively regulated the MEG3/p53 axis in a DNMT3b-dependent manner to promote tumor growth. UXT, a novel DNMT3b-binding protein, aggravates the progression of breast cancer through MEG3/p53 axis.

Role of CD147 in regulating the RSK2/Slug/EMT pathway in diabetic foot ulcer healing. / CD147调控RSK2/Slug/EMTé€šè·¯å½±å“ç³–å°¿ç— è¶³æºƒç–¡çš„æ„ˆåˆ.

OBJECTIVES: Diabetic foot ulcer (DFU), with a high rate of amputation and mortality, is a serious complication of diabetes. However, the therapeutic effect of diabetic foot is poor. This study aimed to investigate the effect of CD147 on epithelial-mesenchymal transition (EMT) process in DFU and molecular mechanisms. METHODS: Immunohistochemistry was used to reveal the expression of several proteins, such as CD147, E-cadherin, N-cadherin, Slug, and Phospho-RSK2 in DFU, non-diabetic refractory tissues, and wound margin tissues (normal blood glucose). Western blotting was used to analyze the expression of CD147 and Slug in HaCaT cells in the high-glucose environment. HaCaT cells with CD147 or RSK2 knockdown was constructed. Wound healing assay was used to test the migration capability of HaCaT cells with knockdown of CD147. Western blotting was used to detect the protein level of Slug in HaCaT cells with CD147 or RSK2 knockdown to investigate the effects of CD147 or RSK2 on EMT. Immunoprecipitation (IP) assay was used to detect the interaction between CD147 and RSK2. RESULTS: The expression levels of CD147 and Slug in the epithelial cells of marginal DFU tissues were significantly lower than those in non-diabetic refractory tissues and wound margin tissues (all P<0.05). CD147 and Slug expressions were down-regulated in HaCaT cells cultured with high glucose (all P<0.05). The migration ability of HaCaT cells with CD147 knockdown was decreased. Knockdown of CD147 or RSK2 significantly inhibited the expression of Slug. The direct interaction between RSK2 and CD147 was found via IP assay. CONCLUSIONS: CD147 could cause DFU re-epithelialization obstacle via affecting RSK2-mediated Slug/EMT process, which might be an underlying mechanism for the slow healing of DFU.

Household financial burden among multidrug-resistant tuberculosis patients in Guizhou province, China: A cross-sectional study.

Multidrug-resistant tuberculosis (MDR-TB) threatens global public health. Poor access to health care due to financial hardship contributes to further transmission of the disease. The study aimed to:A cross-sectional study was conducted in 2 hospitals designated for MDR-TB from January to August 2018. Data were collected by interviewing eligible MDR-TB outpatients and reviewing the medical records. The magnitude of financial burden was documented by total cost and distribution of cost components. Catastrophic payments were measured by 2 indicators: catastrophic health expenditure (CHE) and catastrophic total costs (CTC), both of which were estimated by incidence and intensity. Their associated factors were determined using logistic regression models.Of 161 households affected by MDR-TB, the average total costs due to MDR-TB treatment in the first year was US$ 8266 and consisted of 72% direct medical costs, 5% direct non-medical costs and 23% indirect costs (income loss). Thirty seven percent of direct medical costs were covered by insurance. Overall, the incidence of CHE and CTC was 68.3% and 87.0%, respectively. Both incidence and intensity for the 2 defined catastrophic costs increased when a households income decreased. Five significant factors of catastrophic costs were low household income, absence of students in a family, hospital length of stay, male gender, and job/productivity loss.Households with MDR-TB patients shouldered a high financial burden which was mainly driven by direct medical costs and income loss in Guizhou. Greater catastrophic payments were associated with hospital length of stay and socioeconomic status, especially had a dose-response relationship with households income. Our findings suggest that financial and social protection of local policies for MDR-TB should be improved by preparing a uniform and comprehensive insurance package to cover sufficiently direct medical costs, and introducing social pro-poor assistance policies for risk families to protect them from financial hardship.

Drug Non-Adherence And Reasons Among Multidrug-Resistant Tuberculosis Patients In Guizhou, China: A Cross-Sectional Study.

PURPOSE: Treatment interruption and incorrect dosage for measuring drug non-adherence have seldom been studied in multidrug-resistant tuberculosis (MDR-TB) treatment. This study aimed to 1) estimate the overall and drug-specific incidence of short (≤14 days) and serious (>14 days) treatment interruption among MDR-TB patients, 2) identify main reasons and predictors for serious interruption, and 3) document the level of agreement of classification for incorrect drug dosage between self-report and pill count. PATIENTS AND METHODS: A cross-sectional study combining hospital-based interviews and home-based pill count was conducted from January to June 2018. Treatment interruption was determined from patient's medical records and interviews using a structured questionnaire among 202 patients treated at one designated hospital for MDR-TB treatment. Concordance of pills counted with self-reports for each drug use within one month was assessed for a subgroup of patients at their homes using kappa statistics. RESULTS: Of 202 patients, the incidence of short and serious treatment interruption was 37.6% and 28.7%, respectively. Adverse drug reactions (ADRs) and financial hardship were the top two reasons for serious interruption. Amikacin and cycloserine had the highest rate of specific drug interruption (18.3% and 10.2%, respectively). ADRs (ORadj: 2.82, 95% CI: 1.41-5.61), monthly out-of-pocket expenses exceeding 250 US dollars (ORadj: 2.27, 95% CI: 1.14-4.50), and baseline co-morbidities (ORadj: 2.53, 95% CI: 1.19-5.38) were significantly associated with serious treatment interruption. Of 111 patients assessed for pill count at home, 5.4% had perfect drug adherence, 54.1% had drug under-use, 6.3% had drug over-use, and 34.2% had both problems. The respective number from self-reports was 7.2%, 56.8%, 5.4% and 30.6%. The two methods gave an acceptable level of agreement for most of the drugs (kappa: 0.52-0.95). CONCLUSION: Close monitoring of ADRs, revision of drug regimens, and financial support for MDR-TB in this study population are needed. Self-report on drug under-use and over-use should be monitored monthly in clinical settings.