Factors influencing catastrophic health expenditure of households with people with diabetes in Northwest China-an example from Gansu Province.

BACKGROUND: Diabetes is a chronic non-communicable disease that causes a substantial economic burden on diabetic suffers and their households. The aim of this study was to explore the prevalence, equity, and determinants of catastrophic health expenditure (CHE) among households with people with diabetes in Northwest China. METHODS: A total of 3,000 households were included in the 6th Health services survey in Gansu Province, China of which 270 households with people with diabetes. The equity of CHE was evaluated by concentration curve and concentration index (CI). We adopted the Pareto chart to analyze the main economic intervals of the occurrence of CHE. Finally, we combined the decision tree and logistic model and analyzed the determinants of the occurrence of CHE. RESULTS: The incidence of CHE at 15%, 25% and 40% were 75.19%, 58.89% and 35.19%, respectively. CHE tended to occur in households with a lower economic level, with the phenomenon being more pronounced at Z = 40%. The Pareto chart showed that households in the group with an annual per capita income of 0-740 USD (0-5,000 Chinese Yuan) were most likely to experience CHE. Both decision tree and logistic models suggested that economic level, comorbidities, and small household size were potential risk factors. In addition, the decision tree model also suggested the interaction between the influencing factor of health checks in the past 12 months and the number of chronic diseases. CONCLUSIONS: In summary, Households with people with diabetes were more likely to incur CHE. It is essential to focus on low- and middle-income households with people with diabetes, strengthen the management of patients with diabetes, and provide timely health interventions to reduce the occurrence of chronic comorbidity and the risk of CHE in households.

Carotid Intraplaque Neovascularization Predicts Ischemic Stroke Recurrence in Patients with Carotid Atherosclerosis.

INTRODUCTION: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. METHODS: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. RESULTS: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892-10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410-8.646; p = 0.007). CONCLUSIONS: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

CHD is Associated With Higher Grades of NAFLD Predicted by Liver Stiffness.

BACKGROUND AND AIM: Accumulating clinical and epidemiologic evidence indicates that nonalcoholic fatty liver disease (NAFLD) is not only associated with liver-related morbidity and mortality, but also with a greater risk of coronary heart disease (CHD). However, there is currently no diagnostic parameter for NAFLD that has been determined to reliably indicate the presence of CHD as a co-morbidity. We evaluated the liver stiffness and visceral fat thickness of NAFLD patients ultrasonographically to explore the relationship between liver stiffness, visceral fat thickness, and CHD, aiming to find explore the relationship between the liver stiffness and CHD. METHODS: We enrolled 120 consecutive patients who had been initially diagnosed with CHD on the basis of their symptoms. All patients underwent coronary angiography or computed tomography angiography, and were classified into a CHD group and a non-CHD group on the basis of the results. All patients underwent liver ultrasonography, shear-wave elastography, and visceral fat thickness measurement. RESULTS: NAFLD and visceral fat thickness were significantly positively correlated with CHD and Gensini score (P<0.001). Multivariate regression showed that age, male, cholesterol, liver stiffness, and visceral fat thickness were determinants of CHD. Age, cholesterol, liver stiffness, and visceral fat thickness cut-off points for the prediction of CHD were above 50 years old [area under the curve (AUC): 0.678; sensitivity, 87%; specificity, 42.6%], >3.76 mmol/L (AUC: 0.687; sensitivity, 68.4%; specificity, 64.8%), >6.1 kPa (AUC: 0.798; sensitivity, 50%; specificity, 92.6%), and >7.41 cm (AUC: 0.694; sensitivity, 52.6%; specificity, 87%), respectively. Compared with the use of age, gender, and cholesterol (model 1), the addition of the liver stiffness cut-off to model 1 resulted in a stronger predictive value (P=0.005). CONCLUSIONS: High-grade NAFLD is more present in symptomatic CHD. The higher degree of liver stiffness in patients with NAFLD, the higher risk of CHD in these NAFLD patients.

Carotid intraplaque neovascularization predicts atherosclerotic renal artery stenosis in patients with carotid artery stenosis.

BACKGROUND AND AIMS: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with atherosclerotic renal artery stenosis (ARAS) in patients with normal kidney function. METHODS AND RESULTS: We investigated carotid IPN using CEUS in 198 consecutive patients with normal kidney function with and without ARAS. IPN was graded on the basis of the presence and location of microbubbles within each plaque (0, no visible microbubbles in the plaque; 1, moderate microbubbles confined to the shoulder and/or adventitial side of the plaque; and 2, extensive microbubbles throughout the plaque). The grades of each plaque were averaged to obtain an overall score per patient. ARAS was determined angiographically. We found that a higher CEUS-assessed carotid IPN score was associated with ARAS (Odd Ratio, OR: 7.281; 95% Confidence Interval, 95% CI: 3.246-16.336; P < 0.001). Furthermore, an IPN score >1.75 predicted severe stenosis with a sensitivity of 81% and specificity of 58%. Compared with using the IPN score alone, the addition of the homocysteine (HCY) cutoff value (>22.5 mmol/L) resulted in a stronger predictive value (Area Under Curve, AUC: 0.893 vs 0.834; P < 0.001) for severe ARAS. CONCLUSION: Carotid plaque neovascularization combined with HCY levels is predictive of severe ARAS in patients with normal kidney function. CEUS-assessed carotid IPN is clinically useful for stratification of ARAS in patients with normal kidney function.

Association between Nonalcoholic Fatty Liver and Gensini Score in Patients with Coronary Heart Disease: A Cross-Sectional Study.

INTRODUCTION: Obesity is one of the important risk factors of coronary heart disease (CHD). Nonalcoholic fatty liver disease (NAFLD) is always accompanied by obesity. Therefore, this study was designed to elucidate the relationship between NAFLD and CHD in obese and nonobese populations. METHODS: We conducted a cross-sectional study of 454 Chinese patients diagnosed with CHD. Patients were grouped into non-NAFLD + nonobese, non-NAFLD + obese, NAFLD + nonobese, and NAFLD + obese based on the presence or absence of both NAFLD and obesity. RESULTS: The mean Gensini score was significantly higher in patients with fatty liver compared to those without. Logistic regression analysis found that fatty liver, uric acid, and blood glucose levels were risk factors for a high Gensini score. CONCLUSIONS: Irrespective of the presence of obesity, NAFLD is a risk factor for CHD, and the clinical effect of nonobese fatty liver (especially in women) should be carefully considered.

[Isoliquiritigenin can inhibit migration and invasion of human glioma stem cells by down-regulating matrix metalloproteinases].

OBJECTIVE: To investigate the effects of isoliquiritigenin on the migration and invasion of human glioma stem cells and the underlying mechanism. METHODS: The stem cell markers CD133 and Nestin in SHG44 human glioma stem cells were examined with immunofluorescence microscopy. The migration and invasion ability of glioma stem cells was determined by transwell method. The mRNA and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by real-time RT-PCR and Western blot, respectively. RESULTS: CD133 and Nestin were positive in SHG44 cells. The number of migrated cells in SHG44 cells treated with 20 and 80 µmol/L isoliquiritigenin for 48 h were significantly lower than that in control group (76±5 and 42±4 vs. 85±6, all P<0.01), and the number of migrated cells in 80 µmol/L isoliquiritigenin group was lower than that in 20 µmol/L isoliquiritigenin group (P<0.01). The numbers of cells crossing through membrane in 20 and 80 µmol/L isoliquiritigenin groups were 190±13 and 130±9, respectively, which were significantly lower than that in control group (230±14, all P<0.01), and the number of crossed cells in the 80 µmol/L isoliquiritigenin group was lower than that in 20 µmol/L isoliquiritigenin group (P<0.01). The mRNA and protein expression levels of MMP-2 and MMP-9 were decreased compared with control group (P<0.05 or P<0.01), and the expression levels in 80 µmol/L isoliquiritigenin group were lower than those in 20 µmol/L isoliquiritigenin group (P<0.05 or P<0.01). CONCLUSIONS: Isoliquiritigenin exhibits antitumor effects on glioma stem cells by inhibiting cell migration and invasion, which may be related to the down-regulation of MMP-2 and MMP-9.

Multiplexing seven miRNA-Based shRNAs to suppress HIV replication.

Multiplexed miRNA-based shRNAs (shRNA-miRs) could have wide potential to simultaneously suppress multiple genes. Here, we describe a simple strategy to express a large number of shRNA-miRs using minimal flanking sequences from multiple endogenous miRNAs. We found that a sequence of 30 nucleotides flanking the miRNA duplex was sufficient for efficient processing of shRNA-miRs. We inserted multiple shRNAs in tandem, each containing minimal flanking sequence from a different miRNA. Deep sequencing of transfected cells showed accurate processing of individual shRNA-miRs and that their expression did not decrease with the distance from the promoter. Moreover, each shRNA was as functionally competent as its singly expressed counterpart. We used this system to express one shRNA-miR targeting CCR5 and six shRNA-miRs targeting the HIV-1 genome. The lentiviral construct was pseudotyped with HIV-1 envelope to allow transduction of both resting and activated primary CD4 T cells. Unlike one shRNA-miR, the seven shRNA-miR transduced T cells nearly abrogated HIV-1 infection in vitro. Additionally, when PBMCs from HIV-1 seropositive individuals were transduced and transplanted into NOD/SCID/IL-2R γc(-/-) mice (Hu-PBL model) efficient suppression of endogenous HIV-1 replication with restoration of CD4 T cell counts was observed. Thus, our multiplexed shRNA appears to provide a promising gene therapeutic approach for HIV-1 infection.

Purification and characterization of a novel bacteriocin produced by Lactobacillus crustorum MN047 isolated from koumiss from Xinjiang, China.

The growing emergence of antibiotic-resistant bacteria in the food industry needs to be controlled with effective antimicrobials. In this study, bacteriocin MN047 A (BMA) was found to have antibacterial activity against multidrug-resistant bacteria. It was produced by Lactobacillus crustorum MN047, which was first isolated from koumiss, a traditional fermented dairy product from Xinjiang Autonomous Region, China. It was purified by ammonium sulfate precipitation, ion-exchange chromatography, and reversed-phase chromatography. It had a low molecular mass of 1,770.89 Da according to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the sequence was identified as QLPWQILGIVAGMFQA by liquid chromatography-tandem mass spectrometry analysis and MASCOT searching. It was proteinaceous in nature: the bacteriocin was digested by protease but not by α-amylase or lipase. It showed broad pH toleration (pH 2-11), good thermostability, and good storage stability. It had a broad inhibitory spectrum, including both gram-positive and gram-negative bacteria. Growth curve and time-kill kinetics indicated that it was bactericidal to the indicator strains, and this finding was verified by scanning electron microscope and transmission electron microscope after treatment with BMA. As well, BMA halted the growth of Staphylococcus aureus and Escherichia coli in the G1 and G2/M phases according to cell-cycle analysis by flow cytometry, indicating that BMA had comprehensive inhibitory effects against foodborne pathogens.

The mitochondrial translocator protein, TSPO, inhibits HIV-1 envelope glycoprotein biosynthesis via the endoplasmic reticulum-associated protein degradation pathway.

UNLABELLED: The HIV-1 Env glycoprotein is folded in the endoplasmic reticulum (ER), which is necessary for viral entry and replication. Currently, it is still unclear how this process is regulated. The glycoprotein folding in the ER is controlled by the ER-associated protein degradation (ERAD) pathway, which specifically targets misfolded proteins for degradation. Previously, we reported that HIV-1 replication is restricted in the human CD4(+) T cell line CEM.NKR (NKR). To understand this mechanism, we first analyzed cellular protein expression in NKR cells and discovered that levels of the mitochondrial translocator protein TSPO were upregulated by ∼64-fold. Notably, when NKR cells were treated with TSPO antagonist PK-11195, Ro5-4864, or diazepam, HIV restriction was completely disrupted, and TSPO knockdown by short hairpin RNAs (shRNAs) achieved a similar effect. We next analyzed viral protein expression, and, interestingly, we discovered that Env expression was specifically inhibited. Both TSPO knockdown and treatment with TSPO antagonist could restore Env expression in NKR cells. We further discovered that Env proteins were rapidly degraded and that kifunensine, an ERAD pathway inhibitor, could restore Env expression and viral replication, indicating that Env proteins were misfolded and degraded through the ERAD pathway in NKR cells. We also knocked out the TSPO gene in 293T cells using CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeat [CRISPR]/CRISPR-associated-9) technology and found that TSPO could similarly inhibit Env expression in these cells. Taken together, these results demonstrate that TSPO inhibits Env protein expression through the ERAD pathway and suggest that mitochondria play an important role in regulating the Env folding process. IMPORTANCE: The HIV-1 Env glycoprotein is absolutely required for viral infection, and an understanding of its expression pathway in infected cells will identify new targets for antiretroviral therapies. Env proteins are folded in the ER and secreted through the classical secretory pathway. The Env folding process involves extensive cross-linking of 10 Cys residues by disulfide bond formation and heavy N-glycosylation on ∼30 Asn residues. Currently, it is still unclear how this process is regulated. Here, we studied this mechanism in the HIV nonpermissive human CD4(+) T cell line CEM.NKR. We found that Env proteins were rapidly degraded through a cellular pathway that specifically targets misfolded proteins, resulting in inhibition of Env expression. Importantly, we have identified a mitochondrial translocator protein, TSPO, which could trigger this degradation by interfering with the Env folding process. Further characterization of TSPO antiviral activity will reveal a novel antiretroviral mechanism that targets the Env protein.

Positive correlation between neovascularization degree of carotid atherosclerosis determined by contrast-enhanced ultrasound and level of serum C-reactive protein.

BACKGROUND: Neovascularization is one of the most important risk factors for unstable plaque. This study was designed to correlate plaque thickness, artery stenosis and levels of serum C-reactive protein with the degree of intraplaque enhancement determined by contrast-enhanced ultrasound. PATIENTS AND METHODS: Contrast-enhanced ultrasound was performed on 72 carotid atherosclerotic plaques in 48 patients. Contrast enhancement within the plaque was categorized as grade 1, 2 or 3. Maximum plaque thickness was measured in short-axis view. Carotid artery stenosis was categorized as mild, moderate or severe. RESULTS: Plaque contrast enhancement was not associated with the degree of artery stenosis or with plaque thickness. Serum C-reactive protein levels were positively correlated with the number of new vessels in the plaque. C-reactive protein levels increased in the three groups(Grade 1: 3.72±1.79mg/L; Grade 2: 7.88±4.24 mg/L; Grade 3: 11.02±3.52 mg/L), with significant differences among them (F=10.14, P<0.01), and significant differences between each two groups (P<0.05). Spearman’s rank correlation analysis showed that serum C-reactive protein levels were positively correlated with the degree of carotid plaque enhancement (Rs =0.69, P<0.01). CONCLUSIONS: The combination of C-reactive protein levels and intraplaque neovascularization detected by contrast-enhanced ultrasound may allow more accurate evaluation of plaque stability.

Primary cervicothoracic melanoma of spinal cord: a case report and literature review.

A 53-year-old male patient presented progressive numbness and weakness in the right limbs for a 2-year duration. Magnetic resonance imaging scans revealed an intramedullary lesion crossed over cervical and thoracic levels accompanied by syringomyelia at the proximal end of the lesion. The patient underwent subtotal resection of the neoplasm. The histological findings of the tumor were consistent with primary intramedullary malignant melanoma and not initial ependymoma after careful dermatologic and ophthalmologic re-examination. Primary melanoma of the spinal cord, particularly cervicothoracic localization with syringomyelia, is seldom reported in the literature. We report a case of this uncommon tumor and also discuss the clinical course, diagnosis, and treatment.

Associations of mixed metal exposure with chronic kidney disease from NHANES 2011-2018.

Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.

Anti-hepatocellular carcinoma activity of Sorbaria sorbifolia by regulating VEGFR and c-Met/apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorbaria sorbifolia (SS) is a traditional Chinese medicine (TCM) that has been employed anti-hepatocellular carcinoma (HCC) for over 2000 years; yet, its underlying mechanism is still not fully understood. AIM OF THE STUDY: In this study, we evaluated the anti-HCC effect on the freeze-dried powder of the water extract of SS (FDSS) by inhibiting tumor-induced neovascularization, and promoting apoptosis, and elucidated the underlying mechanisms. MATERIALS AND METHODS: HCC cell lines (HepG2 and Huh7 cells) and HepG2 xenograft tumors in zebrafish were employed as in vivo and in vitro models, respectively, to evaluate the anti- HCC-indued neovascularization and apoptosis. In HCC cell lines, CCK-8 assay, wound-healing assay, transwell assay, cell circle assay, apoptosis assay, transmission electron microscopy, and co-culture assay were performed in vitro; in HepG2 xenograft tumor-zebrafish, tumor growth inhibition assay, hematoxylin and eosin (HE) staining, xenograft tumor-zebrafish apoptosis assay, and HCC-indued neovascularization assay were performed to evaluate the effect of FDSS on biological behavior of tumor, HCC-indued neovascularization, and apoptosis. The expression of VEGFR and c-Met/apoptotic pathway-related proteins was detected by western blotting analysis. Assays for c-Met and VEGFR activation were conducted to assess the impact of FDSS in either agonistic or inhibitory roles on these receptor proteins. RESULTS: The findings from our study revealed that FDSS effectively suppresses the proliferation, migration, and invasion of HepG2 and Huh7 cells, as well as inhibiting tumor growth in the HepG2 xenograft zebrafish model by downregulating the expression of p-Met and p-AKT proteins. FDSS decreased the tumor growth associated with promoting apoptosis, including arresting HepG2 and Huh7 cells cycle at G0/G1phase, increasing apoptotic cell numbers and apoptotic bodies in cancer cells, and increasing the apoptotic fluorescence of xenograft tumor zebrafish by downregulating Bcl-2 proteins and upregulating Bax, caspase-9, and caspase-3 levels. We also found that FDSS can inhibit HCC-induced neovascularization and regulate VEGFR. Using an agonist or inhibitor of c-Met and VEGFR in HepG2 cells, we discovered that FDSS can downregulate c-Met and VEGFR protein expression. CONCLUSION: FDSS exerts an anti-HCC effect by inhibiting HCC-indued neovascularization and pro-apoptosis through the inhibition of the action of VEGFR and c-Met/apoptotic pathway.

Identification of molecular determinants from Moloney leukemia virus 10 homolog (MOV10) protein for virion packaging and anti-HIV-1 activity.

Discovery of novel antiretroviral mechanism is essential for the design of innovative antiretroviral therapy. Recently, we and others reported that ectopic expression of Moloney leukemia virus 10 (MOV10) protein strongly inhibits retrovirus replication. MOV10, a putative RNA helicase, can be packaged into HIV-1 virions by binding to the nucleocapsid (NC) region of Gag and inhibit viral replication at a postentry step. Here, we report critical determinants for MOV10 virion packaging and antiviral activity. MOV10 has 1,003 amino acids and seven helicase motifs. We found that MOV10 packaging requires the NC basic linker, and Gag binds to the N-terminal amino acids 261-305 region of MOV10. Our predicted MOV10 three-dimensional structure model indicates that the Gag binding region is located in a structurally exposed domain, which spans amino acids 93-305 and is Cys-His-rich. Simultaneous mutation of residues Cys-188, Cys-195, His-199, His-201, and His-202 in this domain significantly compromised MOV10 anti-HIV-1 activity. Notably, although MOV10-Gag interaction is required, it is not sufficient for MOV10 packaging, which also requires its C-terminal all but one of seven helicase motifs. Moreover, we have mapped the minimal MOV10 antiviral region to amino acids 99-949, indicating that nearly all MOV10 residues are required for its antiviral activity. Mutations of residues Cys-947, Pro-948, and Phe-949 at the C terminus of this region completely disrupted MOV10 anti-HIV-1 activity. Taken together, we have identified two critical MOV10 packaging determinants and eight other critical residues for anti-HIV-1 activity. These results provide a molecular basis for further understanding the MOV10 antiretroviral mechanism.

Parasitoid-induced changes in metabolic rate and feeding activity of the emerald ash borer (Coleoptera: Buprestidae): implications for biological control.

Parasitoid-host interactions form the foundation of biological control strategies against many agriculture and forest insect pests. The emerald ash borer (EAB), Agrilus planipennis (Coleoptera: Buprestidae), is a serious invasive pest of ash (Fraxinus spp.) trees in North America. Tetrastichus planipennisi (Hymenoptera: Eulophidae) is a gregarious, koinobiont endoparasitoid, attacking late (3rd to 4th) instars of EAB larvae, which feed in the live phloem of ash trunks or branches, making serpentine-like galleries filled with larval frass. In the present study, we tested the hypothesis that T. planipennisi regulates the host metabolism and feeding activity to optimize its offspring development and fitness. We first compared the respiration rate of parasitized and unparasitized host larvae at different times after parasitism, and then measured feeding activity of both parasitized and unparasitized host larvae inside their feeding galleries. Although parasitized host larvae increased metabolic rate and feeding activity in the first few days of parasitism, T. planipennisi parasitism induced an overall reduction of the metabolic rate and decrease in feeding activity of parasitized host larvae over their development period. In addition, there was a negative relationship between feeding activity of parasitized hosts and brood sizes of the parasitoid progeny-i.e., the more parasitoid progeny a host larva received, the less feeding activity the host had. These findings suggest that T. planipennisi has limited ability to optimize its offspring development and fitness through regulations of the host metabolism and feeding activity and its parasitism reduces feeding damage of parasitized EAB larvae to infested ash trees.

Exploring the factors influencing the use of health services by people with diabetes in Northwest China: an example from Gansu Province.

BACKGROUND: Diabetes is associated with high morbidity, mortality and quality-of-life impairment in patients. In China, the number of people suffering from diabetes ranks first in the world. Gansu Province is located in northwest China and is an economically underdeveloped region of China. By analyzing the level of health service utilization of people with diabetes in Gansu Province, the degree of equity in health service utilization and its influencing factors were studied to provide scientific data to support the promotion of health equity for people with diabetes and the introduction of relevant policies by relevant authorities. METHODS: A sample of 282 people with diabetes who were 15 years old and above was chosen by multi-stage stratified sampling method. A structured questionnaire survey was conducted via face-to-face interviews. Random forest and logistic regression analysis were used to demonstrate the effects of the explanatory variables on health seeking behaviors from predisposing, enabling and need variables. The concentration index was used to indicate the equity of health service utilization across households of different economic levels. RESULTS: The outpatient rate for the diabetic population surveyed was 92.91%, with 99.87% of urban patients, higher than the 90.39% of rural patients. The average number of hospital days per person was 3.18 days, with 5.03 days per person in urban areas, which was higher than the 2.51 days per person in rural areas. The study showed that the factors most likely to influence patients to seek outpatient services were frequency of taking diabetic medication, whether or not they were contracted to a household doctor, and living environment; the top three factors most likely to influence patients with diabetes to seek inpatient services were number of non-communicable chronic disease, self-assessment of health status, medical insurance. The concentration index for outpatient service utilization and inpatient service utilization were - 0.241 and 0.107, respectively, indicating that outpatient services were concentrated on patients at lower income levels and patients at higher income levels tended to favor inpatient services. CONCLUSION: This study found that the low level of health care resources available to people with diabetes, whose health status is suboptimal, makes it difficult to meet their health needs. Patients' health conditions, comorbidities of people with diabetes, and the level of protection were still important factors that hindered the use of health services. It is necessary to promote the rational use of health services by diabetic patients and further improve the corresponding policies to achieve the goal of chronic disease prevention and control in "Health China 2030".

Associations of urinary and blood cadmium concentrations with all-cause mortality in US adults with chronic kidney disease: a prospective cohort study.

Epidemiological evidence for the relationship between cadmium exposure and mortality in specific chronic kidney disease (CKD) populations remains scarce. We aimed to explore the relationships between cadmium concentrations in urine and blood and all-cause mortality among CKD patients in the USA. This cohort study was composed of 1825 CKD participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2014) who were followed up to December 31, 2015. All-cause mortality was ascertained by matching the National Death Index (NDI) records. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in relation to urinary and blood cadmium concentrations by Cox regression models. During an average follow-up period of 82 months, 576 CKD participants died. Compared with the lowest quartiles, HRs (95% CIs) for all-cause mortality associated with the fourth weighted quartiles of urinary and blood cadmium concentrations were 1.75 (1.28 to 2.39) and 1.59 (1.17 to 2.15), respectively. Furthermore, the HRs (95% CIs) for all-cause mortality per ln-transformed IQR increment in cadmium concentrations in urine (1.15 µg/g UCr) and blood (0.95 µg/L) were 1.40 (1.21 to 1.63) and 1.22 (1.07 to 1.40), respectively. Linear concentration-response relationships between urinary and blood cadmium concentrations and all-cause mortality were also found. Our findings suggested that increased cadmium concentrations in both urine and blood significantly contributed to enhanced mortality risk in CKD patients, thus highlighting that efforts to reduce cadmium exposure may reduce mortality risk in high-risk populations with CKD.

Association and interactions between mixed exposure to trace elements and the prevalence of kidney stones: a study of NHANES 2017-2018.

Background: The association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between elements are unclear. The aim of this study was to explore the association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between the elements. Methods: A total of 1,244 participants (139 kidney stone formers and 1,105 non-stone former participants) in NHANES 2017-2018 were included. The exposure to trace elements was evaluated by measuring their concentration in urine samples. Three methods, Logistic regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR), were used for analysis. Results: According to the results from qgcomp and BKMR, a negative association was found between exposure to the 13 trace elements and the prevalence of kidney stones [OR = 0.50 (0.32, 0.78)]. Subgroup analysis revealed that Co, As, and iodine in the whole population, Co, As, and Ni in males, and Cs, iodine, and Sb in females, were most strongly associated with kidney stones. Kidney stone was found to be positively correlated with Co and negatively correlated with the other elements. Besides, there were significant interactions between Ni and Pb in the whole population, Co and iodine in males, and Pb and iodine in females. Conclusion: There was a negative association between exposure to the mixture of 13 trace elements and the prevalence of kidney stones.

Evidence for Vpr-dependent HIV-1 replication in human CD4+ CEM.NKR T-cells.

BACKGROUND: Vpr is exclusively expressed in primate lentiviruses and contributes to viral replication and disease progression in vivo. HIV-1 Vpr has two major activities in vitro: arrest of cell cycle in the G2 phase (G2 arrest), and enhancement of viral replication in macrophages. Previously, we reported a potent HIV-1 restriction in the human CD4+ CEM.NKR (NKR) T cells, where wild-type (WT) HIV-1 replication was inhibited by almost 1,000-fold. From the parental NKR cells, we isolated eight clones by limiting dilution. These clones showed three levels of resistance to the WT HIV-1 infection: non-permissive (NP), semi-permissive (SP), and permissive (P). Here, we compared the replication of WT, Vif-defective, Vpr-defective, and Vpu-defective viruses in these cells. RESULTS: Although both WT and Vpu-defective viruses could replicate in the permissive and semi-permissive clones, the replication of Vif-defective and Vpr-defective viruses was completely restricted. The expression of APOBEC3G (A3G) cytidine deaminase in NKR cells explains why Vif, but not Vpr, was required for HIV-1 replication. When the Vpr-defective virus life cycle was compared with the WT virus life cycle in the semi-permissive cells, it was found that the Vpr-defective virus could enter the cell and produce virions containing properly processed Gag and Env proteins, but these virions showed much less efficiency for reverse transcription during the next-round of infection. In addition, although viral replication was restricted in the non-permissive cells, treatment with arsenic trioxide (As2O3) could completely restore WT, but not Vpr-defective virus replication. Moreover, disruption of Vpr binding to its cofactor DCAF1 and/or induction of G2 arrest activity did not disrupt the Vpr activity in enhancing HIV-1 replication in NKR cells. CONCLUSIONS: These results demonstrate that HIV-1 replication in NKR cells is Vpr-dependent. Vpr promotes HIV-1 replication from the 2nd cycle likely by overcoming a block at early stage of viral replication; and this activity does not require DCAF1 and G2 arrest. Further studies of this mechanism should provide new understanding of Vpr function in the HIV-1 life cycle.

Analysis of human APOBEC3H haplotypes and anti-human immunodeficiency virus type 1 activity.

Human APOBEC3H (A3H) has one cytidine deaminase domain (CDD) and inhibits the replication of retrotransposons and human immunodeficiency virus type 1 (HIV-1) in a Vif-resistant manner. Human A3H has five single amino acid polymorphisms (N15Δ, R18L, G105R, K121D, and E178D), and four haplotypes (I to IV) have previously been identified in various human populations. Haplotype II was primarily found in African-derived populations, and it was the only one that could be stably expressed. Here, we identified three new haplotypes from six human population samples, which we have named V, VI, and VII. Haplotypes V and VII are stably expressed and inhibit HIV-1 replication. Notably, haplotype V was identified in samples from all African-, Asian-, and Caucasian-derived populations studied. Using haplotype VII, we investigated the A3H anti-HIV-1 mechanism. We found that A3H virion packaging is independent of its CDD but dependent on a (112)YYXW(115) motif. This motif binds HIV-1 nucleocapsid in an RNA-dependent manner, and a single Y112A mutation completely disrupts A3H virion incorporation. We further studied the mechanism of A3H resistance to Vif. Although the previously identified APOBEC3G Vif-responsive motif (128)DPDY(131) is not conserved in A3H, placement of this motif into A3H does not make it become less resistant to HIV-1 Vif. We conclude that stably expressed A3H haplotypes may be more broadly distributed in humans than previously realized, and A3H protein is resistant to Vif. These results have important implications for the role of A3H in retrotransposon and HIV-1 inhibition.