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NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
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Humanos , NAD/metabolismo , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Nicotinamida Fosforribosiltransferasa/metabolismo , Citocinas/metabolismo , Quinonas , OxidorreductasasRESUMEN
Adoptive transfer of tumor antigen-specific CD8+ T cells can limit tumor progression but is hampered by the T cells' rapid functional impairment within the tumor microenvironment (TME). This is in part caused by metabolic stress due to lack of oxygen and glucose. Here, we report that fenofibrate treatment of human ex vivo expanded tumor-infiltrating lymphocytes (TILs) improves their ability to limit melanoma progression in a patient-derived xenograft (PDX) mouse model. TILs treated with fenofibrate, a peroxisome proliferator receptor alpha (PPARα) agonist, switch from glycolysis to fatty acid oxidation (FAO) and increase the ability to slow the progression of autologous melanomas in mice with freshly transplanted human tumor fragments or injected with tumor cell lines established from the patients' melanomas and ex vivo expanded TILs.
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Objective:To integrate the best evidence of non-drug intervention of urinary incontinence in elderly women and to formulate practical recommendations.Methods:In this systematic review study, using “elderly woman”,“urinary incontinence”,“bladder training”,“pelvic floor muscle training”,“enuresis”,“leakage of urine” as the key words, the 6S evidence resource pyramid model was used to search in British Medical Journal best practice, Uptodate, World Health Organization, Guidelines International Network, National Institute for Health and Care Excellence, Chinese Medical Association, Scottish Intercollegiate Guideline Network, Registered Nurses Association of Ontario, Cochrane Library, The Joanna Briggs Institute (JBI), New Zealand Guidelines Group, Polish Society of Gynecologists and Obstetricians, PubMed, Embase, Medline, Web of Science, SinoMed, China National Knowledge Infrastructure, WanFang Data, etc. The evidence retrieved included evidence-based knowledge base resources, clinical practice guidelines, expert consensus, systematic review, etc. Data were retrieved from January 1, 2017 to May 1, 2022, and collated from May 2, 2022 to May 25, 2022. Two researchers independently evaluated the quality of literature and extracted data using the AGREE Ⅱ and JBI evidence-based health care center assessment tools. The JBI evidence-based health care center′s evidence pre-rating system and evidence recommendation rating system were applied to rank the evidence; and under the guidance of the evidence structure of JBI, the strength of evidence recommendation was determined and the best evidence was extracted and summarized in combination with the study group discussion and expert opinion.Results:A total of 9 articles were retrieved, including 7 guidelines and 2 systematic reviews; and 6 guidelines were classified as Grade A and 1 as grade B; both 2 systematic reviews were rated as Grade A; 84% (27/32) of the items were evaluated as “Yes”. Evidence were summarized as 34 pieces of best evidence from 6 dimensions, including “overall recommendation, evaluation of type and degree of urinary incontinence, lifestyle change, behavioral therapy, prevention of precipitating factors, intervention in special population”; the flow chart of screening, evaluation, special symptoms, life style and behavior therapy was combed, and the practical suggestions were formed.Conclusions:The overall quality of the literature on non-drug intervention of urinary incontinence in elderly women is high, and the level of evidence is high. Early identification of urinary incontinence types and assessment of disease severity, lifestyle changes, avoidance of predisposing factors and behavioral therapy are the key to non-drug treatment of urinary incontinence in those patients.
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@#Objective To investigate the surgical strategies and clinical efficacy of transmitral septal myectomy in the treatment of recurrent left ventricular outflow tract obstruction (LVOTO) after alcohol septal ablation. Methods The clinical data of patients with recurrent LVOTO after alcohol septal ablation from July 2020 to July 2021 in the Department of Cardiac Surgery, Guangdong Provincial People's Hospital were retrospectively analyzed. Patients were preoperatively evaluated by echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, 3D modeling and printing technology. A personalized surgical strategy was preoperatively developed according to multimodality imaging assessment, while visual exploration was performed on the digital model and simulated surgical resection was performed on the printed model. Results Two female patients were enrolled, aged 62 years and 64 years, respectively. Totally endoscopic transmitral extended myectomy was successfully performed on both patients with aortic cross-clamping time of 96 min and 85 min, respectively. LVOTO was relieved immediately (subaortic peak pressure gradient decreased from 100 mm Hg to 4 mm Hg and from 84 mm Hg to 6 mm Hg, respectively) and the mitral regurgitation significantly improved after the procedure. No patient had complete atrioventricular block or required permanent pacemaker implantation. The patients were discharged uneventfully without postoperative complications. Conclusion Personalized totally endoscopic transmitral extended myectomy combined with multimodality imaging assessment and 3D modeling and printing has an acceptable clinical effect in patients with recurrent LVOTO after alcohol septal ablation. The procedure can precisely resect the hypertrophic septal myocardium while avoiding serious complications such as septal perforation or complete atrioventricular block.
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OBJECTIVE@#To explore the genetic basis for a child with succinate semialdehyde dehydrogenase deficiency.@*METHODS@#Peripheral blood samples of the proband and his parents were collected and subjected to Sanger sequencing. High-throughput sequencing was used to verify the gene variants. Bioinformatic software was used to analyze the pathogenicity of the variant sites.@*RESULTS@#Sanger sequencing showed that the proband carried a homozygous c.1529C>T (p.S510F) variant of the ALDH5A1 gene, for which his mother was a carrier. The same variant was not detected in his father. However, high-throughput sequencing revealed that the child and his father both had a deletion of ALDH5A1 gene fragment (chr6: 24 403 265-24 566 986).@*CONCLUSION@#The c.1529C>T variant of the ALDH5A1 gene and deletion of ALDH5A1 gene fragment probably underlay the disease in the child. High-throughput sequencing can detect site variation as well as deletion of gene fragment, which has enabled genetic diagnosis and counseling for the family.
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Niño , Humanos , Lactante , Errores Innatos del Metabolismo de los Aminoácidos/genética , Discapacidades del Desarrollo , Mutación , Succionato-Semialdehído Deshidrogenasa/genéticaRESUMEN
@#Objective To study the clinical characteristics of patients with partial and transitional atrioventricular septal defects (P/TAVSDs) in our hospital, and to evaluate the early follow-up outcomes from a real-world research perspective. Methods The clinical data of all patients diagnosed with P/TAVSDs from January 1, 2018 to July 12, 2020, in our hospital were collected, and all patients' examination results were used as the real-world follow-up data, univariable Cox risk proportional model was used to analyze the outcomes. A total of 93 patients were finally included in the analysis, 72 with partial and 21 with transitional AVSD. There were 38 males and 55 females at age of 182.0 months (20.0 d to 779.5 months). Results Univariable Cox proportional risk model suggested that at least one cardiac malformation (HR=15.00, 95%CI 3.00 to 75.00, P=0.001), preoperative moderate or greater mitral regurgitation (HR=6.60, 95%CI 1.70 to 26.00, P=0.007), and preoperative moderate or greater tricuspid regurgitation (HR=13.00, 95%CI 3.10 to 51.00, P<0.000 1) were risk factors for moderate or greater postoperative atrioventricular valve regurgitation. Conclusion Children with coarctation of the aorta or partial pulmonary vein connection, moderate or greater preoperative mitral regurgitation, and moderate or greater preoperative tricuspid regurgitation need to be alerted to the risk of moderate or greater postoperative atrioventricular valve regurgitation. Real-world data, with relaxed statistical P values and combined expertise, can suggest clinical conclusions that are close to those of high-quality retrospective studies.
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@#Cardiovascular diseases are the leading cause of death and their diagnosis and treatment rely heavily on the variety of clinical data. With the advent of the era of medical big data, artificial intelligence (AI) has been widely applied in many aspects such as imaging, diagnosis and prognosis prediction in cardiovascular medicine, providing a new method for accurate diagnosis and treatment. This paper reviews the application of AI in cardiovascular medicine.
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Drug target discovery is the basis of drug screening.It elucidates the cause of disease and the mechanism of drug action,which is the essential of drug innovation.Target discovery performed in biological sys-tems is complicated as proteins are in low abundance and endogenous compounds may interfere with drug binding.Therefore,methods to track drug-target interactions in biological matrices are urgently required.In this work,a Fe3O4 nanoparticle-based approach was developed for drug-target screening in biofluids.A known ligand-protein complex was selected as a principle-to-proof example to validate the feasibility.After incubation in cell lysates,ligand-modified Fe3O4 nanoparticles bound to the target protein and formed complexes that were separated from the lysates by a magnet for further analysis.The large surface-to-volume ratio of the nanoparticles provides more active sites for the modification of chemical drugs.It enhances the opportunity for ligand-protein interactions,which is beneficial for capturing target proteins,especially for those with low abundance.Additionally,a one-step magnetic separation simplifies the pre-processing of ligand-protein complexes,so it effectively reduces the endogenous interference.Therefore,the present nanoparticle-based approach has the potential to be used for drug target screening in biological systems.
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OBJECTIVE@#To explore the genetic basis for a child with 46,XY disorders of sex development (DSD) and explore its genotype-phenotype correlation.@*METHODS@#The child was subjected to whole exome sequencing (WES), and exons 1 to 7 of NR5A1 were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis.@*RESULTS@#The patient presented with rudimentary vulva of a female with Tanner stage 1. B-mode ultrasonography has detected ovary and uterus. The child was found to have a chromosome karyotype of 46,XY. WES revealed that the patient has harbored heterozygous deletion of exon 5 of the NR5A1 gene, which was a novel pathogenic variant inherited from the mother. No abnormality was found in the father.@*CONCLUSION@#The main symptoms of 46,XY DSD children are insufficient external genitalia masculinization, for which variants of the NR5A1 gene are an important cause. WES has improved the detection rate of genetic variants and provided a solid basis for genetic counseling of the affected families.
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Niño , Femenino , Humanos , Trastorno del Desarrollo Sexual 46,XY/genética , Trastornos del Desarrollo Sexual/genética , Exones/genética , Pruebas Genéticas , Heterocigoto , Mutación , Factor Esteroidogénico 1/genéticaRESUMEN
BackgroundThe novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown. Methods84 hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were respectively enrolled in this study. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls. FindingsWe found that the levels of TT3 and TSH were lower in COVID-19 patients than control groups (p<0{middle dot}001). Within the group of COVID-19 patients, 61.9% patients (52/84) presented with thyroid function abnormalities. We found a larger proportion of patients in severe condition exhibited thyroid dysfunction than mild/moderate cases (74{middle dot}6% vs. 23{middle dot}8%, p < 0{middle dot}001). Patients with thyroid dysfunction tended to have increased interval time for negative conversion of viral nucleic acid (14{middle dot}1 {+/-} 9{middle dot}4 vs. 10{middle dot}6 {+/-} 8{middle dot}3 days, p = 0{middle dot}088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0{middle dot}001) and increased CRP (p = 0{middle dot}002). In 7 patients with dynamic changes of thyroid function, we observed the levels of TT3 and TSH gradually increased and reached normal range without thyroid hormone replacement at Day 30 post-admission. The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time. InterpretationsThyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be caused by virus attack and damage to the thyroid-pituitary axis. Therefore, more attention should be paid to thyroid function during treatment of COVID-19, and close follow-up is also needed after discharge. FundingThis study was supported by Zhejiang Provincial Science and technology department key R & D plan emergency project (No. 2020c03123-8).
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Background@#Phototherapy is an important method to treatvitiligo. However, it is unclear how phototherapy affectsmelanocyte precursors and skin neural crest stem cells. @*Objective@#To investigate the underlying mechanisms of narrow-band ultraviolet B (NB-UVB) induced melanocyte lineagedifferentiated from human scalp-derived neural creststem cells (HS-NCSCs). @*Methods@#HS-NCSCs were expandedfrom scalp hair follicles. The c-Kit−/CD57− HS-NCSCs wereisolated by cell sorting. Different doses of NB-UVB wereused to irradiate these HS-NCSCs. Cell ultrastructure was examinedby transmission electron microscope. Melanocytemarker expression was analyzed by Quantitative RT-PCRand Western blot. Cell proliferation and migration were alsoevaluated. @*Results@#The c-Kit−/CD57− HS-NCSCs expressedembryonic NCSC biomarkers. NB-UVB at a dose of 100 mJof NB-UVB had little effect on the cell proliferation of differentiatedmelanocytes from c-Kit−/CD57− HS-NCSCs, while700 mJ inhibited cell proliferation significantly. The dendriticprocesses of differentiated melanocytes increased afterradiation. The tyrosinase and Melanocortin 1 receptor (Mc1R)expression of differentiated melanocytes increased after NB-UVB exposure. The effect of NB-UVB on tyrosinase expressionwas modulated by signaling inhibitors H89 andPD98059 as well as Mc1R level in the cells. The migrationability of differentiated melanocytes was enhanced under100 mJ exposure. @*Conclusion@#These data demonstrate thatNB-UVB facilitates melanocytic differentiation of the HSNCSCsand enhances migration of these cells. Mc1R andcAMP pathway play a critical role in NB-UVB induced melanocyticdifferentiation.
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@#Objective To analyze the pathogenic CAPN3 gene mutations in a pedigree affected with limb-girdle muscular dystrophy type 2A.Methods Genomic DNA was extracted from the peripheral blood samples collected from the proband and family members.The whole exome sequencing was used to detect the pathogenic gene in the proband.Suspected mutations were validated by Sanger sequencing.Results The whole exome sequencing showed that the proband carried compound heterozygous mutations of c.1194-9A>G and c.1437C>T (p.ser479=).The c.1194-9A>G was inherited from his mother.The same compound heterozygous mutation was also found in other patients in the family.The proband’s sister and daughter without disease were carriers of c.1437C >T (p.ser479=),and there was no variation detected in his son-in-law.Conclusion The compound heterozygous mutations of the CAPN3 gene were probably responsible for the limb-girdle muscular dystrophy type 2A in the family.
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OBJECTIVE@#To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing.@*RESULTS@#The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers.@*CONCLUSION@#The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.
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Niño , Femenino , Humanos , Amidohidrolasas/genética , Pueblo Asiatico/genética , Exones , Errores Innatos del Metabolismo/genética , Mutación , LinajeRESUMEN
Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.
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OBJECTIVE@#To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic.@*METHODS@#The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method.@*RESULTS@#Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing.@*CONCLUSIONS@#The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.
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Filtros de Aire/virología , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/prevención & control , Desinfección/normas , Equipo Reutilizado/normas , Pandemias/prevención & control , Neumonía Viral/prevención & control , SARS-CoV-2 , Esterilización/normasRESUMEN
Objective@#Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.@*Methods@#A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.@*Results@#The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05).@*Conclusions@#The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.
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OBJECTIVE@#To carry out genetic testing for two families affected with cobalamin C (cblC) and establish a rapid method for the detection of a hotspot pathogenic variant c.609G>A of the MMACHC gene by using a PCR-high-resolution melting curve (PCR-HRM) method.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Potential variants of the MMACHC gene was analyzed by Sanger sequencing. The c.609G>A variant of the MMACHC gene was screened among 100 healthy children with the PCR-HRM method.@*RESULTS@#Sanger sequencing revealed that proband 1 carried compound heterozygous variants c.394C>T and c.609G>A of the MMACHC gene, while proband 2 carried compound heterozygous variants c.482G>A and c.609G>A of the same gene. PCR-HRM analysis of the two probands and the 100 healthy children were consistent with the Sanger sequencing.@*CONCLUSION@#c.609G>A is a hotspot pathogenic variant of the MMACHC gene. The diagnosis of cblC may be rapidly attained through detection by PCR-HRM.
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OBJECTIVE@#To analyze the clinical and molecular characteristics of a child with very long chain acyl-CoA dehydrogenase deficiency (VLCADD).@*METHODS@#Peripheral blood sample of the patient was collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out for the proband. Suspected mutations were validated by Sanger sequencing.@*RESULTS@#The patient, a 12-month-old girl, was admitted for diarrhea, vomiting, fever, poor spirit and decreased blood pressure. During the course of the disease, she also manifested hypertrophic cardiomyopathy, cardiogenic shock, elevated myocardial enzyme kinase, fever and metabolic acidosis, and had died after three days due to ventricular tachycardia and respiratory failure. Genetic testing showed that she has carried heterozygous mutations of of the ACADVL gene, namely c.664G>A (exon 8) and c.1056_1057del (exon 10). Blood screening for metabolic genetic diseases showed increased C12, C14, C16, C18, C14:1, C14:2, C16:1, C4/C3 and C8/C3, accompanied with decreased C0, C0/C16 and C8/C10. VLCADD and secondary carnitine deficiency could not be excluded, which was in keeping with the result of genetic testing.@*CONCLUSION@#The child was diagnosed with VLCADD, which may be attributed to the compound heterozygous c.664G>A and c.1056_1057del variants of the ACADVL gene.
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Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Coprococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.
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Objective To explore the effect of quality control circles (QCCs) in improving the delivery health checkup report.Methods QCC was founded with the theme of"improving the quality of health checkup report delivery."First,we planned an activity schedule and identified topics.We then set target focuses for service personnel,distribution modes,and operating environments;planned countermeasures;and selected optimal policies.Circle members implemented the optimal policies jointly.Reports of physical examinations by the Guoyu health management center were selected and analyzed.The total number of reports before improvement (January to December 2015) was 59 189 of which 34 549 (58.4%) were male patients and 24 640 (41.6%) were female patients;their average age was (37.7± 11.4) years.The total number of reports after improvement (December 2016 to January 2017) was 6 568,of which 3 881 (59.1%) were male patients and 2 687(40.9%) were female patients;their average age was (39.9± 11.7) years.We compared the quality indicators and evaluated the comprehensive quality of the patients before and after improvement.A total of 65 531 physical examination reports of subjects examined at the center between February and December 2017 were selected for effect tracking,including 39 230 (59.9%) men and 26 301(40.1%) women,aged (38.1±11.5).Results The on-time delivery rate of the health examination reports from rose from 51.4% to 94.0%.The ratio of system leakage to sign for reports decreased from 14.5% to 0.8%.The average time between the examination and when each report was handed over to for distribution decreased from 29.8 hours to 4.2 hours,and the average time between each report being distributed to the providers checking in dropped from 509.8 hours to 72.8 hours,while the average time for the preparation of each report for delivery decreased from 13.5 seconds to 3.1 seconds.The average time between delivery of a report and its being signed decreased from 4.3 seconds to 0.1 seconds.Before the improvement,the expected goals were not met.After improvement,the delivery rate of the health examination reports was 100.0%,the delivery intact rate of the group reports was 100.0%,and the satisfaction rate of the group reports was 99.4%.The comprehensive quality for the members was obviously higher after the improvement than before.After 11 months of tracking,the delivery accuracy rate of health examination report still failed to reach the target value of 100.0%,but all other indicators reached the target value,with good results.Conclusions Application of QCC not only improved the delivery the health checkup reports,but also promoted service quality after medical examinations and ended medical dispute caused by the loss of physical examination reports.