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1.
Altern Ther Health Med ; 29(6): 248-253, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37295013

ABSTRACT

Context: Myelodysplastic syndrome (MDS) is a group of highly heterogeneous, malignant clonal diseases derived from hematopoietic stem cells. PD-1 monoclonal antibodies can have a synergistic effect with hypomethylating agents (HMAs), especially for patients with drug resistance to demethylation drugs. TCM in the treatment of MDS can improve hematological indexes, and for some patients, control the proliferation of primitive cells and delay or even block the transformation to leukemia. Objective: The study intended to examine the therapeutic effects of programmed cell death-1 (PD-1) inhibitors and azacitidine combined with the Yisuifang Thick Decoction in the treatment of MDS with older, high-risk patients. Design: The research team performed five prospective case studies. Setting: The study took place at the East Hospital affiliated with Beijing University of Chinese Medicine in Beijing, China. Participants: Participants were five older, high-risk MDS patients at the hospital who received PD-1 and azacitidine combined with Yisuifang Thick Decoction between April 2020 and June 2021. Outcome Measures: The research team measured: (1) treatment duration, (2) curative effects, (3) myelosuppression, (4) immune-related adverse reactions, (5) ending outcomes, and (6) progression-free survival (PFS). Results: The male to female ratio for the five participants was 3:2, and the median age was 69 years, with a range from 62 to 79 years. Four participants had refractory HR-MDS and one had primary MDS. The median treatment duration was 3 months, with a range from 2 to 4 months, and the median progression-free survival (PFS) was 5 months, with a range from 3 to 14 months. All participants achieved a partial response (PR) or a complete remission with incomplete count recovery (CRi) and showed improvement in serological indexes. Conclusions: Older, high-risk MDS patients generally have poor physical conditions, often accompanied by a poor karyotype prognosis and a poor prognosis for survival. Therefore, the combination of PD-1, azacytidine, and Yisuifang Thick Decoction may be an effective way to treat HR-MDS.


Subject(s)
Myelodysplastic Syndromes , Aged , Female , Humans , Male , Middle Aged , Asian People , Azacitidine/therapeutic use , Leukemia/prevention & control , Myelodysplastic Syndromes/drug therapy , Programmed Cell Death 1 Receptor , China
2.
Article in Chinese | WPRIM | ID: wpr-885682

ABSTRACT

Objective:To Clone the silencer sequences of human stimulator of interferon genes (STING) and evaluate its activity in HEK293T and HeLa, and to preliminarily investigate the transcriptional regulatory mechanisms, screening and verifying the possible binding elements for the silencer sequences of STING.Methods:The human STING-5-1a(-124~+ 267, transcription start site, TSS: 0) and STING-5-2a(-124~+ 168) regions were amplified by PCR, subcloned into pGL3-Basic plasmid, and the luciferase activity was detected in HEK293T and HeLa; the human STING silencer region STING-5-1b(+ 169~+ 267) was subcloned into the pGL3-Control plasmid (pGL3-C-5-1b-positive/negative) and STING-5-1b is divided into two complementary elements, subcloned into pGL3-Control vector, named pGL3-C-STING 5-1b-α(+ 169~+ 209) and pGL3-C-STING-5-1b-β(+ 210~+ 267), detecting the relative luciferase activity of the above plasmid in HEK293T and HeLa. Using bioinformatics methods to predict the transcription factor binding site of human STING silencer, make site-directed mutagenesis at the predicted binding site, and detect luciferase activity. Knockdown of THAP1 and TEAD1 by a siRNA strategy and detect the expression level of STING by western blot analysis. Chromosome immunoprecipitation assay further verified the binding of transcription factor to hSTING silencer.Results:It was verified that plasmids mentioned above were constructed correctly by nucleotide sequencing. The relative luciferase increased after truncating the STING-5-1b(+ 169~+ 267) fragment. The relative luciferase activity of pGL3-C-5-1b-positive recombinant plasmid decreased ( P<0.05), compared with pGL3-Control plasmid. Among them, STING-5-1b-β(+ 210~+ 267) fragment play a major inhibitory role. Using bioinformatics software to predict that the transcription factors PR domain zinc finger protein 4 (PRDM4), Thanatos-associated protein 1 (THAP1), TEA Domain Transcription Factor 1 (TEAD1), Nuclear receptor subfamily 4 group A member 1 (NR4A1), Krueppel-like factor 4 (KLF4) and Forkhead box protein O3(FOXO3) may bind to the human STING silencer region (+ 210~+ 267). After transfecting the mutant recombinant plasmid of the transcription factors into HEK293T and HeLa, the relative luciferase activity of THAP1-Mut and TEAD1-Mut were significantly increased, suggesting that STING silencers may contain binding sites of THAP1 and TEAD1. Knockdown of THAP1 and TEAD1 by a siRNA strategy significantly enhanced the transcription activity. Chromosome immunoprecipitation assay showed that the transcription factors TEAD1 and THAP1 combined with hSTING silencer region in the cells. Conclusions:The hSTING silencer luciferase reporter plasmid was successfully constructed. By the activity comparison, it is speculated that the core silencer region of human STING is located in the + 210~+ 267 element, which may contain several potential transcription factor binding sequences.The potential binding sites for transcription factors that may be contained in the DNA, and use Western blot and chromosome immunoprecipitation assays to further confirm the combination of transcription factors TEAD1 and THAP1 with hSTING silencer, laying the foundation for subsequent research.

3.
Article in Chinese | WPRIM | ID: wpr-864842

ABSTRACT

Objective:to explore the effect of improved nursing intervention on bowel preparation before operation in children with common congenital megacolon.Methods:A total of 72 children with long-segment type congenital megacolon underwent surgery in our hospital from June 2016 to June 2019 were enrolled, and divided into two groups by random number table methods, each with 36 cases. Control group received the routine nursing, while the observation group received the routine nursing combined with modified nursing intervention. The enema effect, enema efficiency, enema pain level, complications, and nursing satisfaction were compared between the two groups.Results:The excellent rate of enema in the observation group was higher than that in the control group [94.44% (34/36) vs. 75.00% (27/36), χ2 value was 5.181, P<0.05]. The enema time and the amount of enema fluid in the observation group were significantly lower than those in the control group [(25.39±5.24)min vs. (21.31±3.94)min; (3 628.11±315.24)ml vs (2 842.33±266.18)ml; t value was 3.743, 11.428, P<0.05]. The VAS score of the observation group was significantly lower than that of the control group [(3.39±1.02) vs. (2.18±0.74), t value was 5.761, P<0.05]; the incidence of complications in the observation group was lower than that of the control group [2.87%(1/36) vs. 16.67%(6/36), χ2 value was 2.532, P>0.05]; the satisfaction degree of family members of the observation group was higher than that of the control group [97.22% (28/36) vs 77.78% (35/36); χ2 value was 4.581, P<0.05]. Conclusions:Application of modified nursing intervention can effectively improve the effect and efficiency of enema, reduce the pain and complications for children with long-segment type congenital megacolon, which also obtains high satisfaction degree among family members.

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