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  • 2020-2024  (4,620)
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  • 2020-2024  (4,620)
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  • 1
    In: MedComm, Wiley, Vol. 4, No. 2 ( 2023-04)
    Abstract: Interleukin 37 (IL‐37), a member of the IL‐1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL‐37 in skin cancer remain unclear. Here, we report that IL‐37b‐transgenic mice (IL‐37tg) treated with the carcinogenic 7,12‐dimethylbenzoanthracene (DMBA)/12‐o‐tetradecylphorbol‐13‐acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103 + dendritic cells (DCs). Notably, IL‐37 induced rapid phosphorylation of adenosine 5‘‐monophosphate (AMP)‐activated protein kinase (AMPK), and via single immunoglobulin IL‐1‐related receptor (SIGIRR), inhibited the long‐term Akt activation. Specifically, by affecting the SIGIRR‐AMPK‐Akt signaling axis, which is related to the regulation of glycolysis in CD103 + DCs, IL‐37 inhibited their anti‐tumor function. Our results show that a marked correlation between the CD103 + DC signature (IRF8, FMS‐like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C‐X‐C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA‐induced skin cancer. In a word, our results highlight that IL‐37 as an inhibitor of tumor immune surveillance through modulating CD103 + DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.
    Type of Medium: Online Resource
    ISSN: 2688-2663 , 2688-2663
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 3021470-1
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  • 2
    In: JAMA Network Open, American Medical Association (AMA), Vol. 4, No. 11 ( 2021-11-30), p. e2136116-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2931249-8
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 15 ( 2022-05-20), p. 1681-1692
    Abstract: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node–positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT] ). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m 2 , once a day] on day 1 and capecitabine [1,000 mg/m 2 , twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P 〈 .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group ( P 〈 .001). CONCLUSION Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: BMC Nephrology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. Methods This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. Results Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m 2 . The extrarenal manifestations included purpura ( n  = 6), arthralgia ( n  = 1), peripheral neuropathy ( n  = 1), and cardiomyopathy ( n  = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) ( n  = 3), membranoproliferative Gn ( n  = 3), and mesangial proliferative Gn ( n  = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM ( n  = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone ( n  = 2) or combined with cyclophosphamide ( n  = 4) or mycophenolate mofetil ( n  = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8–5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m 2 . The median cryocrit decreased to 1.0 (0, 5.75) %. Conclusions The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients’ renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.
    Type of Medium: Online Resource
    ISSN: 1471-2369
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041348-8
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: To describe the clinical features, renal pathology findings and prognosis in patients with mixed cryoglobulinemic glomerulonephritis (Gn) caused by hepatitis B virus (HBV) infection. Method This was a retrospective study including seven Chinese patients with HBV infection associated mixed cryoglobulinemic Gn in a tertiary referral hospital from April, 2016 to March, 2019. The demographic, clinical, pathological characteristics, treatment and follow-up data were collected and analyzed. Results Age at renal biopsy was 47±12 years, including three females and four males. 24hUP was 5.6(3.0, 6.6)g/d and five cases presented with nephrotic syndrome. The median baseline eGFR(CKD-EPI) was 23.5(20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations were: purpura (n=6), arthralgia (n=1), peripheral neuropathy (n=1), and cardiomyopathy (n=1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %, rheumatoid factor was 368(117, 733) IU/ml, C3 was 0.48(0.41, 0.57) g/L, C4 was 0.013(0.003, 0.118) g/L. Renal pathologic findings on light microscopy: endocapillary proliferative Gn (n=3), membranoproliferative Gn (n=3), and mesangial proliferative glomerulonephritis(n=1). Hyaline thrombi were seen in four cases, while crescents were found in two cases. On immunofluorescence microscopy, the predominant types of immunoglobulin deposits were: IgM(n=5), IgA(n=1), and codominance of IgG and IgA(n=1). HBsAg and HBcAg deposits were found in only one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and organized microtubules was seen in only one case. All patients received antiviral medication (entecavir, n=6; lamivudine, n=1). They were given corticosteroid alone(n=2) or combined with cyclophosphamide(n=4) or mycophenolate mofetil(n=1). Two patients received plasmapheresis. The median follow-up time were 18 (6, 37) months. One patient died from pneumonia, and one progressed to end stage of renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR (CKD-EPI) was 55.3 (20.7, 111.8) ml/min per 1.73m2. Conclusion Mixed cryoglobulinemic Gn should be screened for HBV etiologies, especially in HBV-endemic country. Endocapillary proliferative Gn was the common pathologic type, as well as membranoproliferative Gn. Diagnosis and treatment in early stage benefit patients’ renal outcome. Long-term prognosis should be investigated in further studies.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1465709-0
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Journal of Chromatographic Science Vol. 59, No. 9 ( 2021-09-29), p. 823-829
    In: Journal of Chromatographic Science, Oxford University Press (OUP), Vol. 59, No. 9 ( 2021-09-29), p. 823-829
    Abstract: A sensitive high-performance liquid chromatography–tandem mass spectrometry method was established for the simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma. The protein precipitation was used for extraction and the gradient elution of the mobile phase A of water (containing 0.01% formic acid) and the mobile phase B of acetonitrile, and methanol (V:V = 1:1, containing 0.01% formic acid) was used for chromatographic separation on a C18 column. Quantification was performed by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 → m/z 283.3 for sildenafil, m/z 461.4 → m/z 283.2 for N-desmethyl sildenafil, m/z 483.3 → m/z 108.1 for sildenafil-d8 (IS) and m/z 469.2 → m/z 283.3 for N-desmethyl sildenafil-d8 (IS) at the positive ionization mode. The intra- and inter-day relative standard deviations were less than 6.8% and 4.1% for sildenafil and N-desmethyl sildenafil, respectively. Accuracy at four levels ranged from 93.1% to 115.9% for sildenafil and 95.6% to 112.5% for N-desmethyl sildenafil. The present method was sensitive and reliable for simultaneous quantification of sildenafil and its active metabolite and was successfully applied to a pharmacokinetic study of an oral low dose of sildenafil in Chinese healthy volunteers.
    Type of Medium: Online Resource
    ISSN: 0021-9665 , 1945-239X
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2044085-6
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  • 7
    In: Regional Anesthesia & Pain Medicine, BMJ, Vol. 45, No. 12 ( 2020-12), p. 955-963
    Abstract: Gap junctions play a pivotal role in contributing to the formation of astroglial networks and in chronic pain. However, the mechanisms underlying the dysfunction of astroglial gap junctions in chronic pain have not been fully elucidated. Methods Chronic constriction injury (CCI) of the sciatic nerve was used to establish rat neuropathic pain model. C6 cells were used to perform experiments in vitro. Von Frey hairs and Hargreave’s method were used to determine the withdrawal threshold of rats. Protein expression was detected by immunofluorescence and western blotting. Results Astragaloside IV (AST IV) significantly attenuated neuropathic pain and suppressed the excitation of spinal astrocytes in rats with CCI. The antinociceptive effect of AST IV was reversed by the gap junction decoupler carbenoxolone (CBX). AST IV inhibited the high expression of phosphorylated connexin 43 (p-Cx43) and p-c-Jun N-terminal kinase (p-JNK) in spinal cord of rats with CCI. JNK inhibitor alleviated neuropathic pain, which was reversed by CBX. JNK inhibitor decreased the high expression of p-Cx43 in both rats with CCI and tumor necrosis factor-alpha (TNF-α)-treated C6 cells. Additionally, the analgesic effect of AST IV was reversed by the adenosine triphosphate-sensitive potassium (K ATP ) channel blocker, glibenclamide (Glib). Glib abolished the inhibitory effects of AST IV on p-JNK and p-Cx43 both in vivo and in vitro. K ATP channel opener (KCO) mimicked the inhibitory effects of AST IV on p-JNK and p-Cx43 in TNF-α-treated C6 cells. Conclusion Our results indicate that the sciatic nerve CCI induces the dysfunction of gap junctions in the spinal cord by activating K ATP /JNK signaling to contribute to neuropathic pain. AST IV attenuates neuropathic pain via regulating the K ATP -JNK gap junction axis.
    Type of Medium: Online Resource
    ISSN: 1098-7339 , 1532-8651
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2028901-7
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  • 8
    In: The Clinical Respiratory Journal, Wiley, Vol. 17, No. 6 ( 2023-06), p. 568-579
    Abstract: This study investigated the relationship between the glucocorticoid‐induced transcript 1 ( GLCCI1 ) gene variant and the degree of improvement in lung function with inhaled corticosteroids (ICS). Methods We searched the PubMed, Embase, Cochrane Library, CBM, CNKI and Wanfang databases to obtain studies on the GLCCI1 rs37973 variant and the efficacy of ICS in asthma. Results The overall meta‐analysis showed that patients with the GG phenotype (mutant homozygotes) exhibited significantly smaller forced expiratory volume in 1 sec (FEV1) change than patients with the AG phenotype (mutant heterozygous) (MD = −0.08, 95% CI [−0.12, −0.03], P  = 0.001). Compared with the AA phenotype (wild homozygotes), the GG phenotype (MD = −4.23, 95% CI [−6.09, −2.38], P   〈  0.00001) and AG phenotype (MD = −1.92, 95% CI [−2.35, −1.49], P   〈  0.00001) had significantly smaller FEV1%pred changes. The FEV1 change subgroup analysis showed that the GG phenotype group was smaller than the AA phenotype group at 8 (MD = −0.53, 95% CI [−0.91, −0.14], P  = 0.007), 12 (MD = −0.16, 95% CI [−0.30, −0.02], P  = 0.02) and 24 (MD = −0.09, 95% CI [−0.17, −0.01], P  = 0.02) weeks of treatment; the GG phenotype group was smaller than the AG phenotype group at 12 weeks (MD = −0.08, 95% CI [−0.15, −0.01], P  = 0.02). Conclusion This meta‐analysis suggests that the GLCCI1 rs37973 variant affects the efficacy of ICS and that the presence of the G allele attenuates the improvement in lung function with ICS.
    Type of Medium: Online Resource
    ISSN: 1752-6981 , 1752-699X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2442214-9
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  • 9
    In: Journal of Integrative Agriculture, Elsevier BV, ( 2023-5)
    Type of Medium: Online Resource
    ISSN: 2095-3119
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2668746-X
    SSG: 21
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  • 10
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 134, No. 11 ( 2021-04-28), p. 1289-1298
    Abstract: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. Methods: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. Results: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine ( n  = 24), 10-μg vaccine ( n  = 24), or placebo ( n  = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine ( n  = 100 for 0/14 or 0/28 regimens), 10-μg vaccine ( n  = 100 for each regimen), or placebo ( n  = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. Conclusions: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. Trial Registration: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
    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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