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The study aims to explore the clinicopathological features and whether the nonsense mutations of CLCN5 gene have effect on the renal expression of CLC-5 protein and megalin/cubilin complex in children with Dent-1 disease. The clinicopathological features and genetic examination of three patients with Dent-1 disease were investigated. The expression of CLC-5 and megalin/cubilin complex in renal tissues was detected by using immunohistochemistry method. Urinary albumin, α1-microglobulin, β2-microglobulin, retinol binding protein, and calcium levels were measured by immunonephelometry. Urinary calcium and low molecular weight proteinuria (LMWP) were enhanced in three patients, and two presented with nephrotic range proteinuria. Focal glomerular obsolescence, minor tubulointerstitial injury, and focal calcification in corticomedullary junction were found in one patient. Nonsense mutations of CLCN5 gene from their mothers were identified in all three patients with Dent-1 disease; however, the expression of CLC-5 protein was not decreased in renal tubular cells. As the receptor complex of albumin and LMWP reabsorption, the expression of megalin/cubilin in the brush border of proximal tubules was decreased in Dent-1 patients. Even if the renal CLC-5 protein is expressed normally, the reduced expression of megalin/cubilin in the brush border of renal proximal tubules may be helpful to understand the physiopathology of Dent-1 disease with nonsense mutations of CLCN5 gene.

Background: Our previous studies had shown pirfenidone (PFD) not only improved tubulointerstitial fibrosis (TIF) but also inhibited the expression of microRNA-21 (miR-21) in the renal tissue of unilateral urethral obstruction (UUO) rats. This study aims to investigate whether PFD can attenuate TIF through inhibiting miR-21 in UUO rats. Methods: Sprague Dawley rats were divided randomly into sham-operated group, UUO group, and PFD and olmesartan (Olm) treatment groups. Samples were collected on day 14. Expression of miR-21, TGF-β1, Smad3, and Smad7 mRNA in the renal tissue was detected using real-time quantitative PCR. Immunohistochemistry was performed to assess the protein expressions of collagen III, E-cadherin, and α-SMA. Automated capillary Western blotting was used to detect the quantitative expression of TGF-β1, Smad3, p-Smad3, Smad7, collagen III, E-cadherin, and α-SMA in renal tissues. The expression of miR-21 and Smad7 mRNA and the protein levels of collagen III and α-SMA were examined in the miR-21-overexpressing cell line, NRK-52E. Results: Compared with the UUO group, both PFD and Olm inhibited renal tubular dilation, diffused epithelial cell degeneration and necrosis, and reduced renal interstitial edema, inflammatory cell infiltration, and collagen fiber deposition, while no significant difference between PFD group and Olm group. Informatics-based approaches identified Smad7 as a likely candidate for regulation by miR-21. Compared with the sham group, miR-21 expression was upregulated in the UUO group resulting in the downregulation of Smad7 expression due to degradation. The overexpression of miR-21 in the in vitro model downregulated Smad7 and promoted EMT and ECM accumulation. Protein levels of TGF-β1, Smad3, p-Smad3, collagen III, and α-SMA were upregulated, while E-cadherin protein was downregulated in the UUO group than in the sham group. PFD rather than Olm decreased the expression of miR-21 and increased the expression level of Smad7 mRNA and then inhibited the TGF-β1/Smad3 signaling pathway. Olm only downregulated the TGF-β1/Smad3 signaling pathway. Conclusions: PFD improves TIF by downregulating the expression of miR-21, then elevating Smad7, and finally inhibiting the activation of the TGF-β1/Smad3 signaling pathway in UUO rats.

Background Liver fibrosis is the result of diffuse excessive deposition of extracellular matrix (ECM) in liver. Collagen is the main component of extracellular matrix. Absent in melanoma 2 (AIM2) is involved in the formation of inflammsome and plays an important role in inflammatory response. However, it is unclear whether AIM2 is involved in the pathogenesis of liver fibrosis. In the present study, we explored the role of AIM2 in the expression of collagen I. Methods In this study, AIM2 was used to co-culture with HepG2 cells. Cell counting kit-8 (CCK-8) was used to measure cell viability. Real time-quantitative PCR (RT-qPCR) and Western blotting were used to detect collagen I expression at mRNA or protein level, respectively. Then HepG2 cells were treated with caspase activation recruitment domain (ASC), pcDNA(+)-AIM2, small interfering RNA (siRNA) and Z-YVAD-fluoromethylketone (Z-YVAD-FMK) to explore their roles in collagen I expression, respectively. Results The viability of HepG2 cells could be not affected with the increased concentrations of AIM2 and Z-YVAD-FMK. The filamentous prisms and vacuoles of HepG2 cells became more obvious when the concentrations of AIM2 increased to 80ng/ml. The expression level of collagen I increased with the increased concentrations of AIM2. The expression level of collagen I could be also induced by pcDNA(+)-AIM2 vector. The expression level of collagen I could be inhibited by ASC siRNA and Z-YVAD-FMK, respectively. Conclusion Collagen I expression could be induced by AIM2 through ASC/caspase-1 signaling pathway. AIM2 might be involved in the pathogenesis of liver fibrosis through inducing collagen I expression.

Panpan Zhai,1–3 Qian Li,1–3 Ali Hassan Gillani,4 Khezar Hayat,1–3,5 Li Shi,1–3 Siyi Wang,1–3 Fei Peng,1–3 Sen Xu,1–3 Qianqian Du,1–3 Zeyu Cao,1–3 Donald E Morisky,6 Yu Fang1–31Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Center for Drug Safety and Policy Research, Xi’an, People’s Republic of China; 3Shaanxi Center for Health Reform and Development Research, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Pharmacy, Yusra Institute of Pharmaceutical Sciences, Islamabad, Pakistan; 5Institute of Pharmaceutical Sciences, University of Veternary and Animal Sciences, Lahore, Pakistan; 6Department of Community Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA 90095-1772, USAPurpose: Hypertension prevalence is mounting at a great pace in the People’s Republic of China and poses a serious threat to health care systems. Medication nonadherence is one of the key factors in controlling high blood pressure. Our study uses two-arm cluster randomized controlled trial to investigate whether personal consultation by postgraduate pharmacy students and short message services (SMS) is effective in improving medication adherence and blood pressure control.Patients and methods: The trial will involve 384 treated patients in 8 community health care centers (CHCs). The 8 CHCs will be randomly assigned to intervention and control group in a ratio of 1:1. Patients in the intervention group will receive a personal consultation which identifies the barriers to medication adherence and SMS reminders which will be sent at 3-day intervals while patients in the control group will receive standard pharmaceutical care. Personal consultation by pharmacy students will be delivered at months 0 and 3. SMS messages will include educational information about normal blood pressure, complications of hypertension, salt intake, healthy diet, smoking cessation, regular exercise, weight control, antihypertensive medication schedule and treatment. Both groups will be followed for 6 months in order to compare their medication adherence and blood pressure at months 0, 3 and 6. The primary clinical outcome is the change in mean blood pressure and medication adherence measured at baseline, months 3 and 6. Secondary outcome is the proportion of patients reaching controlled blood pressure at months 3 and 6.Discussion: Pharmacy students led consultation will be conducted in the process of physical examination and SMS reminders which is at low cost, may be a feasible way to address the high prevalence of hypertension in the People’s Republic of China.Keywords: medication adherence, hypertension, blood pressure, SMS reminders, personal consultation, community health care centers

The aim was to investigate the diagnostic efficacy of urinary protein/creatinine ratio (UPCR) and factors influencing its substitutability of 24-h urine protein (24hUP) in children with proteinuria. A total of 356 children were recruited, including 149 with non-nephrotic-range proteinuria and 207 with nephrotic-range proteinuria which were further divided into Henoch–Schonlein purpura nephritis (HSPN), lupus nephritis (LN), and primary nephrotic syndrome (PNS). The urine protein and creatinine were measured by routine methods. Bland–Altman analysis was used to test the agreement. Spearman correlation was performed to evaluate the relevance. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of UPCR. Bland–Altman analysis showed there was an excellent agreement between UPCR and 24hUP in each group. Correlations between UPCR and 24hUP were strong in 356 children (r = 0.869) and in the non-nephrotic-range proteinuria group (r = 0.806), but moderate in nephrotic-range proteinuria group (r = 0.586). With the increase of nephrotic-range proteinuria, the correlations between UPCR and 24hUP were decreased further, however, after UPCR was adjusted by 24-h urine creatinine (24hUCr), the correlation coefficient was improved (r = 0.682). In three subgroups with nephrotic-range proteinuria, high correlation coefficient (r = 0.731) was observed in HSPN, but not in LN (r = 0.552) and PNS (r = 0.563). The sensitivity and specificity of UPCR for diagnosing nephrotic-range proteinuria were 89.9 % and 92.2%. UPCR is competent in evaluating proteinuria. The degree of proteinuria, 24hUCr and the underlying pathological types of renal disease may be the important influencing factors in the correlation between UPCR and 24hUP in children with nephrotic-range proteinuria.

Additional file 1.

Background Influenza is a global health threat to older adults, and the influenza vaccine is the most effective approach to prevent influenza infection. However, influenza vaccination coverage among Chinese older adults is far less than in developed countries such as the United States (4.0% vs. 64.9%). This study aims to increase influenza vaccination coverage in Chinese adults ≥60 years using a video-led educational intervention conducted by medical students. Methods A cluster randomized controlled trial will be conducted in 4 districts of Xi’an city, Shaanxi Province, China, using a stratified sampling approach. Adults aged ≥60 years will be recruited from 8 community hospitals. A self-administered questionnaire of knowledge, attitudes, and practices (KAP) will be employed to record the KAP score. During the 6-month interventional period, participants in the intervention group will receive educational videos focused on influenza and influenza vaccination, coupled with a group discussion conducted by the medical students. For those in the control group, no intervention will be provided. The outcomes measured in both groups will be the influenza vaccination coverage and the KAP scores of all participants. Discussion Medical students are more likely to educate older adults about scientific knowledge of influenza and its vaccine compared to clinical practitioners, who, most of the time, remain over-occupied due to the extensive workload. Video-led counseling and education could be a useful option to optimize older adults’ understanding of influenza and influenza vaccination. This eventually could improve the uptake of influenza vaccine among Chinese older adults. Trial registration Chinese Clinical Trial Registry; ChiCTR2000034330; Registered 3rd July 2019.

Background: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public&rsquo, s perspective about COVID-19, including their knowledge, attitude, and practices. Methods: A rapid online survey comprising 21 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann&ndash, Whitney tests, Kruskal&ndash, Wallis tests, and regression analysis were carried out during data analysis. Results: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants. Conclusion: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education.

BACKGROUND Hypertension is one of the leading risk factors for ischemic heart diseases, and high rates of hypertension prevalence have either remained the same or increased in developing countries in recent years. Unfortunately, about 20% to 50% of patients with chronic diseases have been nonadherent to their drug therapy. SMS text messaging and pharmacy student–led consultations have the potential to help patients manage their blood pressure (BP). OBJECTIVE The aim of this study was to assess the effectiveness, feasibility, and acceptability of SMS text messaging and consultation to manage the BP of Chinese patients with hypertension. METHODS We conducted a two-arm cluster randomized controlled trial among patients with hypertension in Xi’an City, Shaanxi Province, China, and recruited 384 patients from 8 community health care centers. Patients were randomized into an intervention group to receive SMS text messages and consultations or into a control group to receive usual care for 3 months. We sent SMS text messages at 3-day intervals and collected data at baseline (including demographics, clinical outcomes, medication complexity, side effects, patient behavior, knowledge about hypertension, BP, and medication adherence) and the 3-month follow-up (including BP, medication adherence, and knowledge about hypertension). RESULTS We assessed 445 patients with hypertension and excluded 61 patients who were not eligible or who had not filled out their questionnaires. The mean age of the patients was 68.5 (SD 7.9) years in the intervention group and 69.4 (SD 9.7) years in the control group, and the sample was primarily female (265/384, 69.0%). Patients in the intervention group showed significant improvements in systolic BP (SBP; mean 134.5 mm Hg, SD 15.5 mm Hg vs mean 140.7 mm Hg, SD 15.2 mm Hg; P=.001), medication adherence (mean 7.4, SD 1.2 vs mean 7.0, SD 1.3; P=.04), and knowledge about hypertension (mean 6.3, SD 0.9 vs mean 5.9, SD 1.2; P=.004) compared with those in the control group. In measures of diastolic BP (DBP), the two arms showed nonsignificant improvements (mean 78.2 mm Hg, SD 9.0 mm Hg vs mean 77.2 mm Hg, SD 10.3 mm Hg; P=.06). In total, 176 patients had controlled BP at the 3-month follow-up (98 patients in the intervention group vs 78 patients in the control group), but it was nonsignificant (P=.08). CONCLUSIONS The use of SMS text messaging and consultation to manage SBP and improve medication adherence is effective, feasible, and acceptable among Chinese patients with hypertension, although a significant difference was not observed with regard to DBP. It is important to maximize the potential of SMS text messaging and consultation by increasing the feasibility and acceptance of mobile interventions and conduct a cost-effectiveness analysis on this method. CLINICALTRIAL Chinese Clinical Trial Registry ChiCTR1900026862; http://www.chictr.org.cn/showproj.aspx?proj=42717.

Objective To evaluate price, availability and affordability of insulin products in Shaanxi Province, western China. Methods We used a simplified and adapted WHO/Health Action International method to obtain the availability and prices of insulin products and five oral anti-diabetic medicines as comparators in public general hospitals and private retail outlets. In addition, we investigated the price components of eight selected insulin products by tracing the supply chain. Results All three kinds of insulin products, prandial, basal and premixed insulin, are 100% available in public hospitals, and have fairly high availability in the private sector (62.5-68.8%). The prices of most insulin products were higher than international reference prices in both sectors (ranging from 0.95 times to 2.33 times). All insulin products were unaffordable as they would cost 3.5-17.1 days' wage of the lowest-paid government workers in Shaanxi. The manufacturer's markup (selling price), which comprised more than 60% of the final price of all insulin products surveyed, was the largest price component. Conclusions Although availability of insulin products was high in public general hospitals and private retail pharmacies, their high price made them unaffordable to diabetes patients, especially low-income patients. The government should increase insurance compensation for those who need these life-saving medicines or decrease the cost of insulin products through negotiation with suppliers.

Background Antimicrobial resistance (AMR) is a major public health issue that the world is facing in the 21st century and implementation of antimicrobial stewardship program (ASP) is one of the recognized approaches to combat AMR. Little is known on the views among Pakistani physicians regarding AMR and the benefits of hospital ASP implementation. This study was aimed to investigate the perception and attitude of physicians about AMR and ASP. Methods Qualitative face-to-face and telephonic interviews were conducted by using purposive sampling method with 22 physicians working in seven tertiary care public hospitals of Punjab, Pakistan. All interviews were audio-recorded and transcribed verbatim. Qualitative software was used, and a thematic analysis conducted. Results Three major themes were identified: (1) the growing concern of AMR in Pakistan, (2) the role(s) of healthcare professionals in antibiotic prescribing and infection control, and (3) managing antibiotic resistance in hospitals. Poor healthcare facilities, insufficient trained medical staff, and inadequate resources were the key barriers in the implementation of ASP in Pakistan. Conclusion Physicians of public sector tertiary care teaching hospitals have shown poor familiarity toward hospital ASPs but the concept of hospital ASPs in Pakistan can be established by using the distinct themes that originated during this study. Overall, the attitude of physicians was positive toward its enforcement in all types of hospital settings including teaching hospitals. Disclosures All authors: No reported disclosures.

Background: Antimicrobial resistance (AMR) is a global threat and the antimicrobial stewardship program (ASP) is a globally used tool to combat AMR. There is little information on the views among Pakistani physicians regarding AMR and the benefits of hospital antimicrobial stewardship implementation. This study was designed to explore the physicians&rsquo, views about ASP. Methods: Qualitative face-to-face and telephonic interviews were conducted by using purposive sampling method with 22 physicians working in seven tertiary care public hospitals of Punjab, Pakistan. All interviews were audio recorded and transcribed verbatim. Qualitative software was used, and a thematic analysis was conducted. Results: Three broad themes were identified: (1) the growing concern of antimicrobial resistance in Pakistan, (2) the role(s) of healthcare professionals in antibiotic prescribing, and (3) managing antibiotic resistance in hospitals. Inadequate resources, poor healthcare facilities, and insufficiently trained medical staff were the major hurdles in ASP implementation in Pakistan. Conclusions: Our study found a poor familiarity of hospital ASP among physicians working in public sector tertiary care teaching hospitals, and a number of distinct themes emerged during this study that could be helpful in establishing the concept of hospital ASP in Pakistan. Overall, physicians showed a positive attitude towards the enforcement of ASP in all healthcare settings, including teaching hospitals.

This paper is concerned with blow-up phenomena and persistence properties for an integrable two-component Dullin-Gottwald-Holm shallow water system. We give sufficient conditions on the initial data which guarantee blow-up phenomena of solutions in finite time for both periodic and nonperiodic cases, respectively. Furthermore, the persistence properties of solutions to the system are investigated.

This paper is concerned with the wave breaking phenomenon for a modified two-component Dullin-Gottwald-Holm shallow water system. We give sufficient conditions on the initial data to guarantee blow-up of solutions in finite time.