High-expression of FABP4 in Tubules is a Risk Factor for Poor Prognosis in DKD Patients.

BACKGROUND: Lipid metabolism imbalance is involved in the mechanism of renal tubular injury in diabetic kidney disease (DKD). Fatty acid binding protein 4 (FABP4) has been reported to participate in cellular lipid toxicity. However, the expression of FABP4 in renal tissues of DKD and its correlation with clinical/ pathological parameters and prognosis have not been studied. METHOD: A retrospective cohort study was conducted in 108 hospitalized Type 2 diabetes (T2D) patients with renal injury, including 70 with DKD and 38 with NDKD (non-DKD). Clinical features, pathological findings, and follow-up parameters were collected. Serum and urine FABP4 were detected by ELISA. An immunohistochemistry stain was used to determine FABP4 in renal tubulointerstitium. A double immunofluorescence stain was employed to assess FABP4- and CD68-positive macrophages. Correlation analysis, logistic regression models, receiver operating characteristic (ROC), and Kaplan-Meier survival curve were performed for statistical analysis. RESULTS: DKD patients had increased expression of FABP4 and ectopic fat deposition in tubules. As shown by correlation analyses, FABP4 expression in renal tubules was positively correlated with UNAG (r=0.589, p=0.044) and ESRD (r=0.740, p=0.004). Multivariate regression analysis revealed that UNAG level was correlated with FABP4 expression level above median value (odds ratio:1.154, 95% confidence interval:1.009-1.321, p=0.037). High-expression of FABP4 in renal tubules of DKD was at an increased risk of ESRD. Increased FABP4 expression in inflammatory cells was also associated with ESRD in DKD. CONCLUSION: High-expression of FABP4 is involved in the pathogenesis of renal tubular lipid injury and is a risk factor for poor prognosis in DKD patients.

Changes in spectrum of biopsy-proven kidney diseases within decade: an analysis based on 10 199 cases from South China.

PURPOSE: To assess the regional epidemiological trends of kidney diseases over time in the South China using renal biopsy-proven cases. METHODS: This retrospective observational cohort study was conducted at the Institute of Nephrology, Second Xiangya Hospital of Central South University, and encompasses all patients diagnosed with kidney disease via biopsy from 2012 to 2021. RESULTS: The study sample consisted of 10 199 native kidneys, with a male-to-female ratio of 0.91:1 and an average age of 38.74 (±14.53) years. Primary glomerular nephropathy, systemic glomerular nephropathy (SGN), tubulointerstitial disease, and hereditary renal diseases accounted for 66.92 (6825)%, 24.49 (2498)%, 8.06 (822)%, and 0.53 (54)%, respectively. The leading pathologies of primary glomerular nephropathy remained the IgA nephropathy. The frequencies of IgA nephropathy and membranous nephropathy increased significantly, whereas the frequencies of minimal change disease and focal segmental glomerulosclerosis decreased (P < .001) between 2017 and 2021 than in the years 2012 and 2016. An earlier onset of membranous nephropathy was observed in the age group of 45-59 years compared to previous studies. The leading pathologies of SGN were found to be lupus nephritis (758 cases, 30.45%) and hypertension nephropathy (527 cases, 21.17%). The frequencies of hypertension nephropathy and diabetic nephropathy increased between 2017 and 2021 compared to 2012 and 2016 (P < .001), gradually becoming the leading pathological types of SGN. In elderly patients diagnosed with nephrotic syndrome, the frequencies of amyloidosis significantly increased (P < .01). CONCLUSION: Our study may provide insights for kidney disease prevention and public health strategies. What is already known on this topic The pathological spectrum of kidney diseases has undergone significant transformations in the past decade, driven by the escalating incidence of chronic diseases. Although there are studies exploring the renal biopsy findings from various regions in China which present both similarities and differences in epidemiology, few large-scale reports from the South China in recent decades were published. What this study adds Our findings reveal the following key observations: (i) increased proportion of middle-aged patients leading to the increasing average age at the time of biopsy；(ii) the frequencies of IgA nephropathy and membranous nephropathy (MN) increased significantly, whereas the frequencies of minimal change disease and focal segmental glomerulosclerosis decreased (P < .001) between 2017 and 2021 than in the years 2012 and 2016; (iii) earlier onset of MN in the age group of 45-59 years old was found in our study; and (iv) a higher frequency of hypertension nephropathy and DN presented over time, and frequency of amyloidosis increased in elderly patients diagnosed with NS. How this study might affect research, practice, or policy This single-center yet a large-scale study of the kidney disease spectrum in South China may provide a reference point for the diagnosis, treatment, and prevention of chronic kidney disease.

Effect of mobile health reminders on tuberculosis treatment outcomes in Shanghai, China: A prospective cohort study.

Background: Poor adherence increases the risk of unfavorable outcomes for tuberculosis (TB) patients. Mobile health (mHealth) reminders become promising approaches to support TB patients' treatment. But their effects on TB treatment outcomes remain controversial. In this prospective cohort study, we evaluated the effect of the reminder application (app) and the smart pillbox on TB treatment outcomes compared with the standard care in Shanghai, China. Methods: We recruited new pulmonary TB (PTB) patients diagnosed between April and November 2019 who were aged 18 or above, treated with the first-line regimen (2HREZ/4HR), and registered at Songjiang CDC (Shanghai). All eligible patients were invited to choose the standard care, the reminder app, or the smart pillbox to support their treatment. Cox proportional hazard model was fitted to assess the effect of mHealth reminders on treatment success. Results: 260 of 324 eligible patients enrolled with 88 using standard care, 82 the reminder app, and 90 the smart pillbox, followed for a total of 77,430 days. 175 (67.3%) participants were male. The median age was 32 (interquartile range [IQR] 25 to 50) years. A total of 44,785 doses were scheduled for 172 patients in the mHealth reminder groups during the study period. 44,604 (99.6%) doses were taken with 39,280 (87.7%) monitored by the mHealth reminders. A significant time-dependent downward linear trend was observed in the monthly proportion of dose intake (p < 0.001). 247 (95%) patients were successfully treated. The median treatment duration of successfully treated patients in the standard care group was 360 (IQR 283-369) days, significantly longer than those in the reminder app group (296, IQR 204-365, days) and the smart pillbox group (280, IQR 198-365, days) (both p < 0.01). Using the reminder app and the smart pillbox was associated with 1.58 times and 1.63 times increase in the possibility of treatment success compared with the standard care, respectively (both p < 0.01). Conclusion: The reminder app and the smart pillbox interventions were acceptable and improved the treatment outcomes compared with the standard care under the programmatic setting in Shanghai, China. More high-level evidence is expected to confirm the effect of mHealth reminders on TB treatment outcomes.

A Study on the Dynamic Forming Mechanism Development of the Negative Poisson's Ratio Elastomer Molds-Plate to Plate (P2P) Forming Process.

This study proposed a dynamic forming mechanism development of the negative Poisson's ratio elastomer molds-plate to plate (P2P) forming process. To dynamically stretch molds and control the microstructural shape, the proposal is committed to using the NPR structure as a regulatory mechanism. The NPR structural and dynamic parallel NPR-molds to control microstructure mold-cores were simulated and analyzed. ANSYS and MATLAB were used to simulate and predict dynamic NPR embossing replication. The hot-embossing and UV-curing dynamic NPR P2P-forming systems are designed and developed for verification. The results illustrated that the dynamic forming mechanism of the negative Poisson's ratio elastomer molds proposed by this study can effectively control microstructure molds. This can effectively predict and calculate the geometrical characteristics of the microstructures after embossing. The multi-directional dynamic NPR microstructural replication process can accurately transfer microstructures and provide high transfer rate-replication characteristics.

Effect of the Xpert MTB/RIF on the detection of pulmonary tuberculosis cases and rifampicin resistance in Shanghai, China.

BACKGROUND: Xpert MTB/RIF (Xpert) is an automated molecular test recommended by World Health Organization (WHO) for diagnosis of tuberculosis (TB). This study evaluated the effect of Xpert implementation on the detection of pulmonary TB (PTB) and rifampicin-resistant TB (RR-TB) cases in Shanghai, China. METHODS: Xpert was routinely implemented in 2018 for all presumptive PTB patients. All PTB patients above 15 years-old identified within the Provincial TB Control Program during the first half of each of 2017 and 2018, were enrolled to compare the difference in proportions of bacteriological confirmation, patients with drug susceptibility test (DST) results for rifampicin (ie, DST coverage) and RR-TB detection before and after Xpert's implementation. RESULTS: A total of 6047 PTB patients were included in the analysis with 1691 tested by Xpert in 2018. Percentages of bacteriological confirmation, DST coverage and RR-TB detection in 2017 and 2018 were 50% vs. 59%, 36% vs. 49% and 2% vs. 3%, respectively (all p-values < 0.05). Among 1103 PTB patients who completed sputum smear, culture and Xpert testing in 2018, Xpert detected an additional 121 (11%) PTB patients who were negative by smear and culture, but missed 248 (23%) smear and/or culture positive patients. Besides, it accounted for an increase of 9% in DST coverage and 1% in RR-TB detection. The median time from first visit to a TB hospital to RR-TB detection was 62 days (interquartile range -IQR 48-84.2) in 2017 vs. 9 days (IQR 2-45.7) in 2018 (p-value < 0.001). In the multivariate model, using Xpert was associated with decreased time to RR-TB detection (adjusted hazard ratio = 4.62, 95% confidence interval: 3.18-6.71). CONCLUSIONS: Integrating Xpert with smear, culture and culture-based DST in a routine setting significantly increased bacteriological confirmation, DST coverage and RR-TB detection with a dramatic reduction in the time to RR-TB diagnosis in Shanghai, China. Our findings can be useful for other regions that attempt to integrate Xpert into routine PTB and RR-TB case-finding cascade. Further study should focus on the identification and elimination of operational level challenges to fully utilize the benefit of rapid diagnosis by Xpert.

Efficacy and effect of free treatment on multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) is a serious public health and social issue. It pertains to the type of tuberculosis that is resistant simultaneously to isoniazid and rifampicin. MDR-TB has a high mortality and is expensive to treat. The aim of the present study was to examine the therapeutic effects of individualized free treatment and the relevant influencing factors on the treatment outcome for MDR-TB. A prospective study module was used to analyze the therapeutic outcome of MDR-TB with individualized free treatment for 160 patients between 2011 and 2014. Statistical analysis was performed using the Chi-square or Fisher's exact test, and the odds ratio was calculated using a logistic regression analysis model. In total, 160 patients were enrolled in the study for treatment of MDR-TB. From these, 88 cases completed the course of treatment, and 70 cases were successfully treated. Of the remaining 72 cases, 37 cases exhibited treatment failure, 18 cases were suspended during treatment and 17 patients succumbed to the disease. The results showed that the confounding factors were: i) retreatment (p<0.05); ii) occurrence of diabetes (p<0.001); iii) lesion without improvement in radiography during treatment (p=0.001); iv) positive sputum culture for Mycobacterium tuberculosis after 3-month treatment (p<0.05); and v) termination of treatment due to adverse reaction (p<0.05). These factors were associated with poor treatment outcomes by logistic regression analysis. Adverse drug reaction was observed in 33 cases and treatment was terminated or changed permanently in 29 of these cases. The most common adverse reaction was liver function damage caused by pyrazinamide and leucopenia caused by rifabutin. One patient suffered from serious liver failure. In conclusion, the success rate of long treatment course for MDR-TB is not high due to many adverse reactions. Occurrence of diabetes is the main factor that caused poor efficacy.

Anti-tuberculosis drug-induced liver injury in Shanghai: validation of Hy's Law.

INTRODUCTION: The most reliable liver safety signal in a clinical trial is considered to be 'Hy's Law cases' defined as subjects experiencing hepatocellular injury and serum bilirubin elevations with no more likely cause than study drug. However, there is little published data to support the current biochemical criteria for Hy's Law cases or their use to estimate postmarketing risk of severe liver injury. OBJECTIVES: The primary objective of this study was to identify and characterize Hy's Law cases in patients treated for tuberculosis (TB). A secondary objective was to identify patient risk factors for drug-induced liver injuries. METHODS: We utilized eDISH (evaluation of Drug-Induced Serious Hepatoxicity) to retrospectively analyze data from 517 patients treated for activeTB, a regimen well known to be capable of causing severe hepatotoxicity. RESULTS: We identified two Hy's Law cases, which is consistent with the treatment's known risk of liver failure. Despite monthly monitoring, neither Hy's Law case experienced a documented elevation in serum alanine aminotransferase exceeding 10 × upper limits of normal. Hepatoprotectant use and infection with chronic hepatitis B were associated with increased risk of liver injury. CONCLUSIONS: Our observations support the current biochemical criteria for Hy's Law cases and their use to estimate postmarketing risk.