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  • Ovid Technologies (Wolters Kluwer Health)  (221)
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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Journal of the American Society of Nephrology Vol. 30, No. 2 ( 2019-2), p. 216-227
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 2 ( 2019-2), p. 216-227
    Abstract: Considerable evidence indicates that basolateral inwardly rectifying potassium channel Kir4.1/Kir5.1 is essential for membrane transport in the distal convoluted tubule (DCT), and that dietary sodium and potassium are important in regulating activity of the thiazide-sensitive Na-Cl cotransporter (NCC). In mouse studies, the authors found that stimulation of NCC induced by sodium restriction was associated with increasing Kir4.1/Kir5.1 activity in the DCT and membrane hyperpolarization; NCC inhibition induced by high sodium intake was associated with decreasing Kir4.1/Kir5.1 activity in the DCT and membrane depolarization. In kidney-specific Kir4.1 knockout mice, the effect of dietary sodium on NCC activity was largely abolished, as were its effects on DCT membrane conductance and potential. The findings indicate that Kir4.1/Kir5.1 is essential for mediating dietary sodium intake–induced modulation of NCC function. Background Dietary sodium intake regulates the thiazide-sensitive Na-Cl cotransporter (NCC) in the distal convoluted tubule (DCT). Whether the basolateral, inwardly rectifying potassium channel Kir4.1/Kir5.1 (a heterotetramer of Kir4.1/Kir5.1) in the DCT is essential for mediating the effect of dietary sodium intake on NCC activity is unknown. Methods We used electrophysiology, renal clearance techniques, and immunoblotting to examine effects of Kir4.1/Kir5.1 in the DCT and NCC in wild-type and kidney-specific Kir4.1 knockout mice. Results Low sodium intake stimulated basolateral Kir4.1/Kir5.1 activity, increased basolateral K + conductance, and hyperpolarized the membrane. Conversely, high sodium intake inhibited the potassium channel, decreased basolateral K + currents, and depolarized the membrane. Low sodium intake increased total and phosphorylated NCC expression and augmented hydrochlorothiazide-induced natriuresis; high sodium intake had opposite effects. Thus, elevated NCC activity induced by low sodium intake was associated with upregulation of Kir4.1/Kir5.1 activity in the DCT, whereas inhibition of NCC activity by high sodium intake was associated with diminished Kir4.1/Kir5.1 activity. In contrast, dietary sodium intake did not affect NCC activity in knockout mice. Further, Kir4.1 deletion not only abolished basolateral K + conductance and depolarized the DCT membrane, but also abrogated the stimulating effects induced by low sodium intake on basolateral K + conductance and hyperpolarization. Finally, dietary sodium intake did not alter urinary potassium excretion rate in hypokalemic knockout and wild-type mice. Conclusions Stimulation of Kir4.1/Kir5.1 by low intake of dietary sodium is essential for NCC upregulation, and inhibition of Kir4.1/Kir5.1 induced by high sodium intake is a key step for downregulation of NCC.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2029124-3
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  • 2
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 71, No. 4 ( 2018-04), p. 622-630
    Abstract: AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr 53 ) by a time-dependent way with the peak at 4 days. PD123319 treatment (4 days) stimulated the basolateral 40 pS K channel activity, augmented the basolateral K conductance, and increased the negativity of distal convoluted tubule membrane. The stimulation of Kir4.1 was essential for PD123319-induced increase in NCC because inhibiting AT2R increased the expression of tNCC and pNCC only in wild-type but not in the kidney-specific Kir4.1 knockout mice. Renal clearance study showed that thiazide-induced natriuretic effect was larger in PD123319-treated mice for 4 days than untreated mice. However, this effect was absent in kidney-specific Kir4.1 knockout mice which were also Na wasting under basal conditions. Finally, application of AT2R antagonist decreased the renal ability of K excretion and caused hyperkalemia in wild-type but not in kidney-specific Kir4.1 knockout mice. We conclude that AT2R-dependent regulation of NCC requires Kir4.1 in the distal convoluted tubule and that AT2R plays a role in stimulating K excretion by inhibiting Kir4.1 and NCC.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2094210-2
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  • 3
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 133, No. 14 ( 2020-06-19), p. 1639-1648
    Abstract: The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients ( n = 144) were randomly divided (1:1) to receive either ETV monotherapy ( n  = 70) or peg-interferon add-on therapy from week 26 to 52 ( n  = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria. Results At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P   〈  0.001; combination therapy: 5.7 [3.0, 18.8] vs . 3.2 [2.0, 4.3] ng/mL, P   〈  0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs . 7.8 [5.4, 11.1] kPa, P  = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs . 4.1% [3/73], P  = 0.809) and HBeAg conversion rate (12.5% [7/56] vs . 11.0% [8/73], P  = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs . 98.5%, P  = 0.150) between the two groups. Conclusions Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy. Trial registration ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 4
    In: Infectious Diseases & Immunity, Ovid Technologies (Wolters Kluwer Health), Vol. 1, No. 1 ( 2021-04), p. 28-35
    Abstract: Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces. Methods: In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality. Results: The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 10 9 /L, neutrophil count of more than 7 × 10 9 /L, lymphocyte count of less than 0.8 × 10 9 /L, platelet count of less than 100 × 10 9 /L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively. Conclusions: We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.
    Type of Medium: Online Resource
    ISSN: 2693-8839
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 3123817-8
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  • 5
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 133, No. 9 ( 2020-02-11), p. 1015-1024
    Abstract: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Abstract: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687] ) but not in the high-risk group ( P 〉 0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e1182717-
    Type of Medium: Online Resource
    ISSN: 2572-9241
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2922183-3
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  • 8
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 2 ( 2017-02-02)
    Abstract: Most cardiovascular diseases occur in low‐ and middle‐income regions of the world, but the socioeconomic distribution within China remains unclear. Our study aims to investigate whether the prevalence of cardiovascular diseases differs among high‐, middle‐, and low‐income regions of China and to explore the reasons for the disparities. Methods and Results We enrolled 46 285 individuals from 115 urban and rural communities in 12 provinces across China between 2005 and 2009. We recorded their medical histories of cardiovascular diseases and calculated the INTERHEART Risk Score for the assessment of cardiovascular risk‐factor burden, with higher scores indicating greater burden. The mean INTERHEART Risk Score was higher in high‐ and middle‐income regions than in low‐income regions (9.47, 9.48, and 8.58, respectively, P 〈 0.0001). By contrast, the prevalence of total cardiovascular disease (stroke, ischemic heart disease, and other heart diseases that led to hospitalization) was lower in high‐ and middle‐income regions than in low‐income regions (7.46%, 7.42%, and 8.36%, respectively, P trend =0.0064). In high‐ and middle‐income regions, urban communities have higher INTERHEART Risk Score and higher prevalent rate than rural communities. In low‐income regions, however, the prevalence of total cardiovascular disease was similar between urban and rural areas despite the significantly higher INTERHEART Risk Score for urban settings. Conclusions We detected an inverse trend between risk‐factor burden and cardiovascular disease prevalence in urban and rural communities in high‐, middle‐, and low‐income regions of China. Such asymmetry may be attributed to the interregional differences in residents’ awareness, quality of healthcare, and availability and affordability of medical services.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 9
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 277, No. 4 ( 2023-04), p. 557-564
    Abstract: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). Background Data: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. Methods: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. Results: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. Conclusions: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.
    Type of Medium: Online Resource
    ISSN: 0003-4932
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2002200-1
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  • 10
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 134, No. 11 ( 2021-05-6), p. 1299-1309
    Abstract: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. Methods: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m 2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR] , stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. Results: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%–81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. Conclusion: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. Clinical trial registration: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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