Changes in tuberculosis burden and its associated risk factors in Guizhou Province of China during 2006-2020: an observational study.

BACKGROUND: Understanding the trends of tuberculosis (TB) burden and its risk factors at the provincial level in the context of global End TB targets is crucial to identify the progress and challenges in TB control. We aimed to estimate the burden of TB and risk factors for death from 2006 to 2020 for the first time in Guizhou Province, China. METHODS: Data were collected from the national TB surveillance system. Four indicators of TB burden and their corresponding age-standardized rates (ASRs), including incidence (ASIR), prevalence (ASPR), mortality (ASMR) and disability-adjusted life years (DALYs) (ASDR), were estimated and stratified by year, age, gender and prefecture. Temporal trends of ASRs were presented by locally weighted regression, and the annual percentage change was calculated. The correlation between gross domestic product (GDP) per capita and ASRs was evaluated by Pearson correlation analysis. The associated risk factors for death in PTB patients were determined using logistic regression models. RESULTS: A total of 557,476 pulmonary TB (PTB) cases and 11,234 deaths were reported, including 2233 (19.9%) TB specific deaths and 9001 (80.1%) deaths from other causes. The 15-year average incidence, prevalence and mortality rates were 94.6, 102.6 and 2.1 per 100,000 population, respectively. The average DALY rate was 0.60 per 1000 population. The ASIR and ASPR have shown downward trends since 2012, with the largest percentage decrease in 2020 (ASIR: -29.8%; ASPR: -30.5%). The number in TB specific deaths consistently decreased during the study period (P<0.001), while the increase in deaths from other causes drove the overall upward trend in ASMR and ASDR. Four ASRs remained high in males and 5 prefectures. GDP per capita was negatively associated with the ASIR, ASPR and ASDR (P<0.05). Among PTB patients, men, patients with no fixed job, those with a low GDP level, patients with increasing age, those previously treated, those with severe symptoms, those transferred in and those receiving directly observed treatment were more likely to suffer death. CONCLUSION: Guizhou has made progress in reducing PTB cases and TB specific deaths over the last 15 years. Targeted interventions are needed to address these risk factors for death in PTB patients and high-risk areas.

Global burden and influencing factors of chronic kidney disease due to type 2 diabetes in adults aged 20-59 years, 1990-2019.

Population structure and lifestyles may have contributed to the epidemiological status of Chronic Kidney Disease due to Type 2 Diabetes (CKD-T2D). This study is a secondary data analysis. Using data from the Global Burden of Disease Study, we describe the changes in CKD-T2D burden and its influencing factors in the population aged 20-59 years from 1990 to 2019. Globally, the incidence, death, and Disability Adjusted Life Years (DALYs) rate of CKD-T2D showed an upward trend and increased with age, and the burden in males was higher than that in females. Population growth and aging were important driving factors for the increase of CKD-T2D DALY burden, while high systolic blood pressure and high body-mass index were the primary attributable risk factors. High body-mass index exhibited higher contributions to high Socioeconomic Development Index (SDI) countries, whereas low SDI countries were more impacted by high systolic blood pressure. The population attributable fraction of CKD-T2D DALY caused by high body-mass index was positively correlated with SDI, while high temperature and lead exposure were negatively correlated. Therefore, strengthening disease screening for people aged 20-59 years and formulating early intervention measures based on the level of socioeconomic development may effectively alleviate the burden of CKD-T2D.

[A method for photoplethysmography signal quality assessment fusing multi-class features with multi-scale series information].

Photoplethysmography (PPG) is often affected by interference, which could lead to incorrect judgment of physiological information. Therefore, performing a quality assessment before extracting physiological information is crucial. This paper proposed a new PPG signal quality assessment by fusing multi-class features with multi-scale series information to address the problems of traditional machine learning methods with low accuracy and deep learning methods requiring a large number of samples for training. The multi-class features were extracted to reduce the dependence on the number of samples, and the multi-scale series information was extracted by a multi-scale convolutional neural network and bidirectional long short-term memory to improve the accuracy. The proposed method obtained the highest accuracy of 94.21%. It showed the best performance in all sensitivity, specificity, precision, and F1-score metrics, compared with 6 quality assessment methods on 14 700 samples from 7 experiments. This paper provides a new method for quality assessment in small samples of PPG signals and quality information mining, which is expected to be used for accurate extraction and monitoring of clinical and daily PPG physiological information.

The development and validation of a patient-reported outcome measure to assess financial hardship among older cancer survivors in China: hardship and recovery with distress survey.

Background: Financial hardship has been described as a patient's economic experiencefollowing cancer-related treatment. Standardized patient-reported outcome measures(PROM) to assess this distress has not been well-studied, especially among older cancer survivors. Objective: The aim of this study was to develop and validate PROM for assessing the financial hardship of older cancer survivors in China. Methods: Items were generated using qualitative interviews and literature review. Items were screened based on Delphi expert consultation and patients' opinions. Item response theory (IRT) and classical test theory (CTT) were used to help reduce items. Retained items formed a pilot instrument that was subjected to psychometric testing. A cut-off score for the new instrument for predicting poor quality of life was identified by receiver operating characteristic (ROC) analysis. Results: Qualitative interviews and literature review generated 135 items, which were reduced to 60 items because of redundancy. Following Delphi expert consultation and patients' evaluation, 24 items with high importance were extracted. Sixteen items were selected due to satisfactory statistical analysis based on CTT and IRT. Ten items were retained and comprised 2 domains after loadings in exploratory factor analysis (EFA). Internal consistency was satisfactory (α = 0.838). Test-retest reliability was good (intraclass correlation, 0.909). The ROC analysis suggested that the cut-off of 18.5 yielded an acceptable sensitivity and specificity. Conclusions: The PROM for Hardship and Recovery with Distress Survey (HARDS) consists of 10 items that specifically reflect the experiences of financial hardship among older Chinese cancer survivors, and it also showed good reliability and validity in clinical settings.

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.

Identification of biomarkers for risk assessment of arsenicosis based on untargeted metabolomics and machine learning algorithms.

BACKGROUND: Long-term exposure to inorganic arsenic may lead to arsenicosis. There are, however, currently no validated metabolic biomarkers used for the identification of arsenicosis risk. This study aims to identify metabolites associated with arsenicosis and establish prediction models for risk assessment based on untargeted metabolomics and machine learning algorithms. METHODS: In total, 105 coal-borne arsenicosis patients, with 35 subjects in each of the mild, moderate, and severe subgroups according to their symptom severity, and 60 healthy residents were enrolled from Guizhou, China. Ultra-high performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS) was utilized to acquire the plasma metabolic profiles of the studied subjects. Statistical analysis was used to identify disease-associated metabolites. Machine learning algorithms and the identified metabolic biomarkers were resorted to assess the arsenicosis risk. RESULTS: A total of 143 metabolic biomarkers, with organic acids being the majority, were identified to be closely associated with arsenicosis, and the most involved pathway was glycine, serine, and threonine metabolism. Comparative analysis of metabolites in arsenicosis patients with different symptom severity revealed 422 altered molecules, where disrupted metabolism of beta-alanine and arginine demonstrated the most significance. For risk assessment, the model established by a single biomarker (L-carnosine) could undoubtedly discriminate arsenicosis patients from the healthy. For classifying arsenicosis patients with different severity, the model established using 52 metabolites and linear discriminate analysis (LDA) algorithm yielded an accuracy of 0.970-0.979 on calibration set (n = 132) and 0.818-0.848 on validation set (n = 33). CONCLUSION: Altered metabolites and disrupted pathways are prevalent in arsenicosis patients; The disrupted metabolism of one carbon and dysfunction of antioxidant defense system may partially be causes of the systematic multi-organ damage and carcinogenesis in arsenicosis patients; Metabolic biomarkers, combined with machine learning algorithms, could be efficient for risk assessment and early identification of arsenicosis.

The Epidemiology and Management of Pediatric AKI in Asia.

Because of the lack of early recognition and referral, the incidence of pediatric acute kidney injury (AKI) in Asia still is underestimated. Although each diagnostic criteria has its own merits, the Kidney Disease Improving Global Outcomes classification now is widely accepted. In Asia, the spectrum of pediatric AKI is wide-ranging, from pediatric AKI in highly sophisticated tertiary-care pediatric intensive care units in resource-rich regions due to advanced procedures such as transplantation, cardiac surgery, and other hospital-acquired causes, to primary care preventable causes, such as infectious diseases, snakebite, and so forth in rural parts of the developing world. The development and application of novel biomarkers, concepts such as the Renal Angina Index and advanced renal replacement therapy have revolutionized the era of treating AKI, but the cost and feasibility are the key determinants, especially in rural areas. In view of availability and expenses, peritoneal dialysis should be the first choice in less-developed areas, however, because of various barriers, it still needs more effort. Effective educational steps to both medical carers and families are needed urgently.

IPDN-China promotes the development of pediatric dialysis in China.

BACKGROUND: In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012. METHODS: Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed. RESULTS: Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT). CONCLUSIONS: The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.

[Interference Detection and Quality Assessment of Pulse Signal on Android Platform].

The collection process of the pulse signal is easily disturbed by the noise, that will reduce the quality of the signal, and affect its applications on the healthy monitoring system. In order to solve this problem, this paper analyzes the causes of the generation of interference during pulse signal acquisition and the characteristics of interference performance, and puts forward the corresponding detection algorithm for pulse signal interference section. Based on this algorithm, a Cascaded Layer-by-Layer Discrimination method is proposed to evaluate the quality of pulse signals, in which pulse signals are divided into available signals and unavailable signals. Experimental results on PC and Android platform show that the proposed algorithm can detect the interference segment accurately in the pulse signal in real time, and improve the usability of the evaluation for pulse signal.

Recent advances and effective strategies in the discovery and applications of natural products.

Natural products are the most representative form of conventional therapy as compared to any other traditional or alternative medicine systems. They have numerous active components, either primary or secondary metabolites, which are associated with the diverse, intricate, and distinct characteristics of natural products and result in various pharmacological effects in clinic. However, some problems are associated with research on herb quality, which is the core of the drug industry, and restrict the development of this field to a certain extent. Quality-markers (Q-markers), a novel concept for quality assessment, open up a new avenue for promotion of healthy development of traditional medicine industry and improvement of the quality standard system to enhance traditional medicine or product quality standards. In this study, we first summarized the main factors affecting the quality of traditional medicines and natural products and importance for safety and then presented the concept of background and relevant factors of Q-markers. Moreover, the modern science technology and related methods used to identify the chemical composition have been discussed. Especially, based on the systematic analysis and discussion of the basic properties and clinical features of natural products, we have discussed new trends and effective strategies for identifying relevant Q-markers from herbs and probed the future research directions and challenges.

[Interference Detection and Signal Quality Assessment of Pulse Signals].

Pulse signal contains a wealth of biological and pathological information. However, it is susceptible to the influence of various factors which results in poor signal quality, and causes the device to generate false alarms. First the pulse signals are processing into discrete symbols, and then compare the test signal with the pulse template by using Dynamic Time Warping (DTW) to get the threshold for which can be used to find the interference segment of the test signal. By analyzing the DTW distance of the pulse signal, we can get the interference degree of the signal, then the quality level of the plus signal can be defined by the relationship between the interference degree and quality of the signal. The 1 055 group pulse signals provided by MIMIC II physiological database are used to train and test the signal quality assessment algorithms, and compared with other existing algorithms. The results show that the algorithms can accurately detect interference segments in pulse signal and reflect the quality of it.

Metabolomics strategy reveals therapeutical assessment of limonin on nonbacterial prostatitis.

Limonin has been found to possess significant anti-inflammatory properties in animal tests and with, human cells, however, its precise metabolism mechanism has not been well explored. The aim of this study was to investigate the anti-inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model. Global metabolite profiling was performed by ultra-high-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC/ESI-TOFMS) and in conjunction with multivariate data analysis and pathway analysis which were integrated to explore differentiating metabolites and clarify the mechanism of limonin against capsaicin-induced NBP. Limonin has a potential protective function revealed by the metabolic profiling of limonin-treated rats located closer to the normal group. Twenty potential biomarker candidates and several key metabolic pathways contributing to the treatment of NBP were discovered and identified. Among the pathways, the related glycine, serine and threonine metabolism, glycerophospholipid metabolism were acutely perturbed. The changes in metabolites were restored to their base-line levels after limonin treatment, which might be through regulating the perturbed pathways to the normal state. The results indicate that changed biomarkers and pathways may provide evidence and insight into limonin action mechanisms and enable us to increase research productivity toward metabolomics in therapeutical assessment and drug discovery.

Salivary proteomics in biomedical research.

Proteins that are important indicators of physiological or pathological states, can provide information for the identification of early and differential markers for disease. Saliva, contains an abundance of proteins, offers an easy, inexpensive, safe, and non-invasive approach for disease detection, and possesses a high potential to revolutionize the diagnostics. Discovery of salivary biomarkers could be used to scrutinize health and disease surveillance. The impact of human saliva proteome analysis in the search for clinically relevant disease biomarkers will be realized through advances made using proteomic technologies. The advancements of emerging proteomic techniques have benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium for the detection of disease. This review presents an overview of the value of saliva as a credible diagnostic tool and we aim to summarize the proteomic technologies currently used for global analysis of saliva proteins and to elaborate on the application of saliva proteomics to the discovery of disease biomarkers, and discuss some of the critical challenges and perspectives in this field.

Good Manufacturing Practices production and analysis of a DNA vaccine against dental caries.

AIM: To prepare a clinical-grade anti-caries DNA vaccine pGJA-P/VAX and explore its immune effect and protective efficacy against a cariogenic bacterial challenge. METHODS: A large-scale industrial production process was developed under Good Manufacturing Practices (GMP) by combining and optimizing common unit operations such as alkaline lysis, precipitation, endotoxin removal and column chromatography. Quality controls of the purified bulk and final lyophilized vaccine were conducted according to authoritative guidelines. Mice and gnotobiotic rats were intranasally immunized with clinical-grade pGJA-P/VAX with chitosan. Antibody levels of serum IgG and salivary SIgA were assessed by an enzyme-linked immunosorbent assay (ELISA), and caries activity was evaluated by the Keyes method. pGJA-P/VAX and pVAX1 prepared by a laboratory-scale commercial kit were used as controls. RESULTS: The production process proved to be scalable and reproducible. Impurities including host protein, residual RNA, genomic DNA and endotoxin in the purified plasmid were all under the limits of set specifications. Intranasal vaccination with clinical-grade pGJA-P/VAX induced higher serum IgG and salivary SIgA in both mice and gnotobiotic rats. While in the experimental caries model, the enamel (E), dentinal slight (Ds), and dentinal moderate (Dm) caries lesions were reduced by 21.1%, 33.0%, and 40.9%, respectively. CONCLUSION: The production process under GMP was efficient in preparing clinical-grade pGJA-P/VAX with high purity and intended effectiveness, thus facilitating future clinical trials for the anti-caries DNA vaccine.

Comparison of quality of life and causes of hospitalization between hemodialysis and peritoneal dialysis patients in China.

BACKGROUND: Hemodialysis (HD) and peritoneal dialysis (PD) are important renal replacement treatment in end stage renal disease (ESRD), but the comparison of quality of life (QOL) and causes of hospitalisation between the two modalities in China is lacking. In the present study, we compared the two modalities in a multi-center study. SUBJECTS AND METHODS: Six hundred and fifty four HD and 408 PD patients were investigated from 10 hospitals in China from Sept, 2004 to Jan, 2005. Among the HD patients, there were 360 males and 294 females with a mean age of 57.22 +/- 12.49 years (18-88 y). Among PD patients, there were 165 males and 243 females, with a mean age of 61.59 +/- 12.65 years (22-89 y). Health related 36 items short form questionnaires (SF-36) were used to assess the quality of life. Hospitalisation data were collected and analyzed. RESULTS: SF-36 domains of Body Pain (BP), General Health (GH), Role-Emotional (RE), Social Functioning (SF), Vitality (VT) and Mental Health (MH) were all significantly higher in the PD patients as compared to the HD patients although there was no significant difference in Physical Functioning (PF) and Role-Physical (RP) between the two groups. The two most common causes of hospitalisation in HD patients were cardiovascular disease (39.8%) and pulmonary infection (21.3%), while they were infectious peritonitis (47.6%) and cardiovascular disease (31.9%) in PD patients. The ever hospitalised patients had lower SF-36 scores in the domains of PF, BP, GH, RE, SF, VT and MH as compared to those of non-hospitalised patients. CONCLUSION: Our study indicated that with the current practice in China, PD patients may enjoy better quality of life than their HD counterparts. Our results also showed that the most common cause of hospitalisation was cardiovascular disease in HD patients and peritonitis in PD patients.

Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese population.

Arsenic and cadmium are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of arsenic and cadmium, but the toxicological interactions of these inorganic mixtures are poorly defined. A general population co-exposed to arsenic and cadmium, was selected in China. The total number of participants was 245, made up of 122 in the arsenic-cadmium polluted area, 123 in the non polluted area. Urinary arsenic (UAs) and cadmium (UCd) were determined by atomic absorption spectrometry as exposure biomarkers and beta2-microglobulin (Ubeta2MG), albumin (UALB), N-acetyl-beta2-glucosaminidase (UNAG) in urine were determined as effect biomarkers. The benchmark dose (BMD) and the lower confidence limit on the benchmark dose (LBMD) were calculated to estimate the critical concentration of UAs and UCd. UAs and UCd concentrations in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The levels of Ubeta2MG, UALB and UNAG in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The BMD/LBMD of UAs and UCd for a 10% level of risk above the background level were estimated as 121.91/102.11 microg/g creatinine and 1.05/0.88 microg/g creatinine. It was suggested that the lower confidence limit of population critical concentration of UAs and UCd for renal dysfunction for 10% excess risk level above the background, which is obtained from LBMD, may need to be kept below 102 and 0.88 microg/g creatinine in order to prevent renal damage in general population co-exposed to arsenic and cadmium. It is indicated that combined effect of arsenic and cadmium were additive effect and/or synergistic effect, and cadmium may potentiate arsenic nephrotoxicity during the long-term and co-exposure to arsenic and cadmium in humans.