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Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-ß (TGF-ß) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.
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Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.
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Electroporación , Inmunoterapia , Vacunas de ADN , Animales , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Electroporación/métodos , Ratones , Inmunoterapia/métodos , Administración Cutánea , Neoplasias/terapia , Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/administración & dosificación , Ovalbúmina/inmunología , Ovalbúmina/administración & dosificación , Células Presentadoras de Antígenos/inmunología , Femenino , Ratones Endogámicos C57BL , Humanos , Vacunación/métodosRESUMEN
Malignant tumors have surpassed stroke and coronary heart disease to become the main cause of death before the age of 70 in the world. The incidence of malignant tumors is increasing year by year, which seriously affects the living standards and social and economic development of Chinese people. Surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy are the main means of Western medicine to intervene in tumors, which are of great significance for prolonging the survival time of patients. However, there are many disadvantages such as adverse reactions and drug resistance. Traditional Chinese medicine has become a research hotspot in recent years because of its definite curative effect and wide application in tumor treatment. Xiao Chaihutang is derived from the Treatise on Febrile and Miscellaneous Diseases. It is composed of Bupleuri Radix, Scutellariae Radix, Ginseng Radix, Pinelliae Rhizoma, Glycyrrhizae Preparata Radix, Ginger, and Jujube. It has the effects of reconciling Shaoyang, reconciling cold and heat Yin and Yang, soothing the liver, and relieving depression. This prescription and the prescriptions based on it are widely used in various stages of tumors. This study summarized the Chinese and foreign research of Xiao Chaihutang in the field of tumors in the past 10 years and explored the role and mechanism of Xiao Chaihutang in blocking precancerous lesions, controlling the development of malignant tumors, reducing the occurrence of adverse reactions after intervention, and alleviating common complications, with a view to expanding the clinical medication ideas.
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Objective To investigate the expression level and diagnostic value of serum DNA polymerase α(DNA pol α)in Alzheimer's disease(AD),and analyze its diagnostic efficacy in AD.Methods A total of 100 patients of dementia of Alzheimer's type(DAT)and 43 patients of mild cognitive impairment(MCI)from Xuanwu Hospital Capital Medical University from March 2019 to April 2023 were included in this study,and 68 healthy individuals of the same age group were collected as the HC group.The expression level of DNA pol α was detected in each group,and the diagnostic value of DNA pol α in AD was analyzed by receiver oper-ating characteristic(ROC)curve.Results The expression level of DNA pol α in DAT group was higher than those in the MCI group(P<0.05)and the HC group(P<0.001).The expression level of DNA pol α showed an increasing trend as AD progressed.The expression level of DNA pol α was negatively correlated with Mini Intelligent Mental State Examination Scale(MMSE)score and Montreal Cognitive Assessment Scale(MoCA)score(r=-0.155 3,-0.203 7,P<0.05).The area under the curve(AUC)of DNA pol α for diagnosing DAT was 0.682,and the sensitivity was 0.900.The AUC for diagnosing MCI was 0.546,and the sensitivity was 0.977.The AUC for differential diagnosis of MCI and DAT was 0.664,the sensitivity was 0.780,and the specificity was 0.535.Conclusion The expression level of DNA pol α is significantly increased in AD patients with DAT,and its expression level is related to the progression of AD,suggesting that DNA pol α has the pos-sibility to be a potential blood biomarker for the diagnosis of AD.
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Objective To study the effect of NAD(P)H:quinone oxidoreductase 1(NQO1)expression lev-el on prognosis in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Methods A total of 103 patients with HBV-HCC underwent surgical treatment in Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine from March 2019 to January 2020 were enrolled.The cancer tissue and adjacent normal tissues were extracted during surgery.Immunohistochemical staining was used to detect the expression of NQO1 in tissues.The clinical and pathological data of patients were collected,and the rela-tionships between high and low expression of NQO1 and pathological characteristics were discussed.A 3-year follow-up was conducted,and the Kaplan-Meier survival curve was drawn and Log-rank test was conducted on median survival time.Then COX model analysis was used to analyze the factors affecting the prognosis of HBV-HCC patients.Results The positive rate of NQO1 in HBV-HCC tissues was 84.47%(87/103)and the high expression rate was 59.22%(61/103).The positive rate and the high expression rate of NQO1 in HBV-HCC tissues were higher than those in adjacent normal tissues(P<0.05).There were statistically significant differences in tumor maximum diameter,number of lesions,American Joint Committee on Cancer(AJCC)staging,and vascular invasion between patients with high and low expression of NQO1(P<0.05).The 3-year follow-up results denoted that the median survival time of patients was 37 months,and no cases were lost in follow-up.Among 103 patients,there were 34 dead cases with an overall survival rate of 66.99%(69/103)and 42 recurrence cases with a recurrence-free survival rate of 59.23%(61/103).Kaplan-Meier survival curve re-sults showed that the overall survival rate and recurrence-free survival rate were 52.46%(32/61)and 50.82%(31/61)in NQO1 high expression group,which were lower than 88.10%(37/42)and 71.43%(30/42)in NQO1 low expression group(P<0.05).COX model analysis results showed that high expression of NQO1,tumor maximum diameter ≥5 cm,multiple lesions,AJCC stage Ⅲ to Ⅳ and vascular invasion were independ-ent risk factors for prognosis(P<0.05).Conclusion NQO1 is highly expressed in HBV-HCC tissue,and is related to the clinicopathological characteristics of patients,so it could be used as an independent biomarker for evaluating prognosis.
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AIM: To observe the distribution of cone in the macular of healthy adult in different ages using adaptive optics scanning laser ophthalmoscope(AO-SLO)system, and analyze its relationship with age.METHODS: A total of 100 healthy examinees(200 eyes)in our hospital from June to July 2023 were selected, and they were divided into four groups according to their age, with 25 cases(50 eyes)in each group, including 18-30 years in group A, 31-40 years in group B, 41-50 years in group C, 51-65 years in group D. AO-SLO was performed in both eyes and cone density was measured.RESULTS: The density of cone in the foveal eccentricity of 3° and 2.4°×2.4° in each group was different(P<0.001), and the cone density in each area showed a relatively regular distribution characteristics, with the highest density in the temporal side, and the temporal>nasal>inferior>superior sides from high to low. The mean cone density in the macular area of both eyes was 14 144.38±1 082.40, 13 241.24±535.32, 12 930.29±727.73, and 10 907.50±490.86 cell/mm2, respectively(P<0.001), indicating that the cone density decreased with age. The correlation analysis showed that the mean cone density in the macular area was negatively correlated with age(r=-0.578, P<0.001).CONCLUSION: AO-SLO is a quantitative non-invasive detection of cones, and there is a negative correlation between cone density and age in healthy human. Furthermore, density of cone in healthy people over 50 years was significantly decreased.
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Overweight/obesity has become an increasingly serious global public health problem. Studies have shown that many factors caused by overweight/obesity are involved in the occurrence of atherosclerosis, including adipokines, inflammatory factors and overweight/obesity related metabolic syndrome. This paper reviews the research progress on overweight/obesity and atherosclerosis from the above perspectives, aiming to provide reference for the prevention of overweight/obesity-related atherosclerosis.
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Cardiovascular diseases are preventable and controllable, and the disease burden caused by them can be reduced after preventive intervention. Attentions should be paid to the prevention of disease causes. For high-risk population, it is necessary to conduct early screening of cardiovascular diseases, control risk factors, reduce exposure level, prevent and control the occurrence or progression of diseases. Clinical prevention services are to evaluate risk factors of health in clinical sites, which can prevent diseases by personalized intervention measures. Clinical prevention services for high-risk population with cardiovascular diseases are generally at a low level in China. This article reviews the early screening, risk factors and clinical prevention services for high-risk population with cardiovascular diseases.
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OBJECTIVE To establish the project approval evaluation system for traditional Chinese medicine (TCM) preparations in medical institutions guided by new drug conversion, to improve the success rate of approval for TCM preparations in medical institutions and lay the foundation for the later drug conversion. METHODS Research and development team used the literature research method and brainstorming method to list and organize relevant elements of project evaluation and determine the initial indicator system. Experts were consulted using the Delphi method to confirm the evaluation index. The weights were calculated based on the proportion of importance scores for each indicator and assigned specific scores to each item. The indicator system was used to evaluate 31 TCM preparations applied for filing by various departments of our hospital from April to July 2023. RESULTS After two rounds of 17 experts’ consultation, the final TCM preparation system included five primary indicators, i.e. theoretical basis, clinical research foundation, pharmaceutical foundation, prescription, and clinical value, as well as 17 secondary indicators including prescription source, traditional Chinese medicine theory, clinical positioning and so on. Human experience was considered as the item which would be rejected as one vote. Based on the above indicator system, our hospital further improved the filing and project approval process for TCM preparations in medical institutions. Among the 31 TCM preparations applied for filing by various departments from April to July 2023, 8 TCM preparations with a score ≥65 were selected for development. CONCLUSIONS The evaluation system is objective, comprehensive, and highly operable. It is suitable for the selection of TCM preparations in medical institutions before research and development.
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AIM: To observe the multimodal imaging characteristics of Best vitelliform macular dystrophy(BVMD).METHODS:The clinical data of 30 patients(60 eyes)diagnosed as BVMD at stage Ⅰ to Ⅳ in Nanjing Medical University Affiliated Eye Hospital from June 2016 to October 2022 were collected for a retrospective analysis, and all patients are binocular involved. All patients underwent best corrected visual acuity(BCVA), slit lamp microscopy, indirect ophthalmoscopy, intraocular pressure, fundus photography, spectral-domain optical coherence tomography(SD-OCT), fundus autofluorescence(FAF), fundus fluorescein angiography(FFA), electro-oculogram(EOG)and optical coherence tomography angiography(OCTA).RESULTS: A total of 30 patients(60 eyes)were included, with 8 eyes at stage Ⅰ, 24 eyes at stage Ⅱ, 22 eyes at stage Ⅲ and 6 eyes at stage Ⅵ. The imaging characteristics of fundus photography, FAF, FFA and SD-OCT were basically consistent with previous literature reports. EOG showed Arden ratio <1.55. OCTA could detect early lesions, observe the location of vitelliform substance, external segment of photoreceptor, fluid and choroidal neovascularization(CNV).CONCLUSION: Multimodal imaging assisted in diagnosing BVMD, reducing missed diagnosis and misdiagnosis, among which OCTA had significant advantages over other examinations, and fast and non-invasive were its biggest advantages.
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Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.
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Acute kidney injury(AKI)is a global public health problem with high morbidity,high mortality and costly treatment cost.The pathogenesis of AKI is very complex,and the treatment strategies for AKI are lim-ited,then it is very matter to explore the pathophysiological mechanism and potential therapeutic targets of acute kidney injury.N6-methyladenosine(m6A)is the most abundant and extremely conservative epigenetic modification in eukaryotic,which is a dynamic and reversible process involving in splicing,nuclear export,translation,stabil-ity,and higher structure of RNA,and regulated by three regulatory factors:methyltransferase,demethylase and methylated reading protein.Current studies have found that m6A plays an important regulatory role in AKI and can be a potential therapeutic target for AKI.In this review,we provide a brief description of m6A and summarize the impact of m6A on AKI and possible future study directions for this research.
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BACKGROUND:Immunotherapy enhances the anti-cancer immune response in many ways,so combined immunotherapy is a better choice.Ultrasound-targeted microbubble destruction technique delivers drugs,genes,antibodies and cytokines directly to the cytoplasm of immune cells and enhances the immune response.However,the application of ultrasound-targeted microbubble destruction technique in the treatment of ovarian cancer with both CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody has not been reported. OBJECTIVE:To investigate the effect of ultrasound irradiation on the proliferation and migration of ovarian cancer cells with CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody double targeted nanobubbles. METHODS:IOSE-80 normal ovarian epithelial cells,SKOV3 and CAOV3 ovarian cancer cells were cultured and expanded.Double labeling fluorescence immunoassay was used to co-locate CXC chemokine receptor 4 and programmed death-ligand 1 protein.Western blot assay was used to detect the relative expression of CXC chemokine receptor 4 and programmed death-ligand 1 protein in three kinds of cells and screen out the experimental cells,i.e.,pure nanobubbles,nanobubbles carrying CXC chemokine receptor 4 antibody,nanobubbles carrying CXC chemokine receptor 4 and programmed death-ligand 1 antibody.SKOV3 ovarian cancer cells in the logarithmic growth phase were taken and divided into six groups for treatment.Group A was added with McCoy's 5A medium.Group B was added with McCoy's 5A medium containing stromal cell-derived factor-1.Group C was added with pure nanobubble solution and McCoy's 5A medium containing stromal cell-derived factor-1.Group D was added with nanobubble solution containing CXC chemokine receptor 4 antibody and McCoy's 5A medium containing stromal cell-derived factor-1.Group E was added with nanobubble solution containing CXC chemokine receptor 4 and programmed death-ligand 1 antibody and McCoy's 5A medium containing stromal cell-derived factor-1.Pure nanobubble solution was added in group F.After ultrasonic irradiation for 120 seconds and incubation for 48 hours,the survival rate of cells was measured by CCK-8 assay,and the healing and migration ability of cells in groups B-E were measured by wound healing test. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that CXC chemokine receptor 4 and programmed death-ligand 1 protein could be expressed in all three kinds of cells.Western blot assay showed that the expression levels of CXC chemokine receptor 4 and programmed death-ligand 1 in SKOV3 and CAOV3 ovarian cancer cells were significantly higher than those in IOSE-80 normal ovarian epithelial cells(P<0.05).(2)CCK-8 assay results exhibited that the cell survival rate of group B was higher than that of group A(P<0.05).The cell survival rate of group F was lower than that of group A(P<0.05).The cell survival rate of groups B-E decreased gradually,and there were significant differences between the two groups(P<0.05).(3)Wound healing test demonstrated that the cell healing rate of groups B-E decreased gradually,and there were significant differences between the two groups(P<0.05).(4)The results show that the use of CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody double targeted nanobubbles under ultrasound-targeted microbubble destruction can significantly inhibit the proliferation and migration of ovarian cancer cells.
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Objective To explore the protection effect and mechanism of preoperative ultrasound-guided stellate ganglion block(SGB)on lung in patients undergoing one-lung ventilation(OLV)during thoracoscopic surgery.Methods Eighty-four patients who underwent OLV during thoracoscopic lobectomy at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2021 to April 2022 were selected as research subjects,and the patients were divided into the observation group and control group by using a random number table,with 42 patients in each group.Patients in the observation group received ultrasound-guided SGB before anesthesia induction,while patients in the control group did not undergo puncture procedures.Patients in both groups received the same anesthesia induction and maintenance protocols.Hemodynamic,respiratory and arterial blood gas parameters were recorded at various time points:upon entering the operating room(T0),before OLV(T1),30 minutes after OLV initiation(T2),60 minutes after OLV initiation(T3),completion of surgery(T4),and 30 minutes after extubation(T5).Oxygenation index(OI),intrapulmonary shunt rate(Qs/Qt)and pH values of patients in the two groups were compared at these time points.Venous blood were collected from patients in both groups at T0,T3 and T5,and enzyme-linked immunosorbent assay was employed to measure the levels of surfactant protein-A(SP-A),superoxide dismutase(SOD),malondialdehyde(MDA),interleukin-6(IL-6)and interleukin-10(IL-10).Postoperative SGB-related complications and pulmonary complications within 72 hours were recorded.Results The mean arterial pressure(MAP)and heart rate(HR)in both groups were significantly lower at T,,T2,and T3 compared to T0(P<0.05);the MAP and HR at T4 and T5 had no statis-tically significant difference compared to those at T0(P>0.05);there was no significant difference in MAP and HR at other time points(P>0.05).MAP in the observation group at T1,T2 and T3 was significantly lower than that in the control group(P<0.05),and HR in the observation group at T2 and T3 was significantly lower than that in the control group(P<0.05);there were no significant differences in MAP and HR between the two groups at other time points(P>0.05).There were no significant differences in pulse oxygen saturation(SpO2)between the two groups at T0-T5(P>0.05).At T2 and T3,peak airway pressure(Ppeak)and respiratory rate(RR)were significantly higher than those at T,and T4,and tidal volume(TV)was significantly lower than that at T,and T4 in both groups(P<0.05).Ppeak and TV in the observation group at T2 and T3 were significantly lower than those in the control group(P<0.05);there were no significant differences in Ppeak and TV between the two groups at T1 and T4(P>0.05).RR and partial pressure of end-tidal carbon dioxide(PetCO2)at T1-T4 showed no significant differences between the two groups(P>0.05).The pH values at T0-T5 showed no significant differences between the two groups(all P>0.05).The OI at T,had no significant difference compared to that at T0 in both groups(P>0.05);OI at T2-T5 in both groups was significantly lower than that at T0(P<0.05);OI in the observation group at T2-T5 was significantly higher than that in the control group(P<0.05).Qs/Qt at T2-T5 was significantly higher than that at T0 and T1 in both groups(all P<0.05);Qs/Qt in the observation group at T2-T5 was significantly lower than that in the control group(P<0.05).At T3 and T5,serum SP-A and IL-6 levels in both groups were significantly higher than those at T0(P<0.05);serum SP-A and IL-6 levels in the observation group at T3 and T5 were significantly lower than those in the control group(P<0.05).At T3 and T5,serum IL-10 level in the control group were significantly lower than that at T0,while serum IL-10 level in the observation group were significantly higher than that at T0(P<0.05).Serum IL-10 level in the observation group at T3 and T5 were higher than that in the control group(P<0.05).At T3 and T5,serum MDA level in the control group was significantly higher than that at T0(P<0.05);serum MDA level in the observation group showed no significant difference compared to that at T0(P>0.05);serum MDA level in the observation group was significantly lower than that in the control group(P<0.05).At T3 and T5,serum SOD level in the control group was significantly lower than that at T0,while serum SOD level in the observation group was significantly higher than that at T0(P<0.05);serum SOD level in the observation group was significantly higher than that in the control group(P<0.05).Four patients in the observation group experienced symptoms of unilateral recurrent laryngeal nerve block,and one patient experienced brachial plexus nerve block,but all improved within 24 hours after surgery.No other adverse reactions were observed during follow-up.Within 72 hours postoperatively,one patient in the control group experienced hypoxemia.Conclusion Preoperative ultrasound-guided SGB has lung-protective effects on patients undergoing OLV in thoracoscopic surgery,which significantly improves OI,reduces intrapulmonary shunts,and inhibits inflammatory response and oxidative stress.
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Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.
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Streptomyces coelicolor , Streptomyces , Streptomyces coelicolor/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Antibacterianos/farmacología , Péptidos/farmacología , Cromosomas , Familia de MultigenesRESUMEN
Compared with a single semiconductor, the heterojunction formed by two different semiconductors usually has higher light utilization and better photoelectric performance. By using stable TiO2 nanotubes as the main subject, CdSe/TiO2NTs heterojunctions were synthesized by a hydrothermal method. XRD, TEM, SEM, PL, UV-vis, and EIS were used to characterize the fabricated CdSe/TiO2NTs. Under visible light irradiation, CdSe/TiO2NTs heterojunctions exhibited a higher absorption intensity and lower degree of photogenerated carrier recombination than TiO2. The electrons and holes were proven to be effectively separated in this heterojunction via theoretical calculation. Under CdSe/TiO2NTs' optimal conditions, the glucose concentrations (10-90 µM) had a linear relationship with the photocurrent value, and the detection limit was 3.1 µM. Moreover, the CdSe/TiO2NTs sensor exhibited good selectivity and stability. Based on the experimental data and theoretical calculations, its PEC sensing mechanism was also illuminated.
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Compuestos de Cadmio , Compuestos de Selenio , Compuestos de Cadmio/química , Compuestos de Selenio/química , Titanio/química , GlucosaRESUMEN
Anemia of inflammation (AI) is associated with inflammatory diseases, and inflammation-induced iron metabolism disorder is the major pathogenic factor. Earlier studies have reported a tendency of AI in periodontitis patients, but the explicit relationship and possible pathological mechanisms remain unclear. Here, the analyses of both periodontitis patients and a mouse model of ligature-induced experimental periodontitis showed that periodontitis was associated with lower levels of hemoglobin and hematocrit with evidence of systemic inflammation (increased white blood cell levels) and evidence of iron restriction (low serum iron along with a high serum hepcidin and ferritin levels), in accordance with the current diagnosis criteria for AI. Moreover, periodontal therapy improved the anemia status and iron metabolism disorders. Furthermore, the increased level of hepcidin and significant correlation between hepcidin and key indicators of iron metabolism emphasized the pivotal role of hepcidin in the pathogenesis of periodontitis-related AI. Administration of the signal transducer and activator of transcription 3 (STAT3) inhibitors Stattic suggested that the IL-6-STAT3-hepcidin signaling pathway participated in this regulatory process. Together, these findings demonstrated that periodontitis should be considered an inflammatory disease that contributes to the development of AI; furthermore, IL-6-STAT3-hepcidin signaling pathway plays a key regulatory role in the pathogenesis of periodontitis-related AI. Our study will provide new insights into the systemic effects of periodontitis, while meaningfully expanding the spectrum of inflammatory diseases that contribute to AI.
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Anemia , Enfermedades Periodontales , Animales , Ratones , Anemia/metabolismo , Anemia/patología , Hepcidinas/metabolismo , Inflamación/patología , Interleucina-6/metabolismo , Hierro/metabolismo , HumanosRESUMEN
Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.
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Objective:To explore the effectiveness of Acute Care of the Elderly(ACE)model and its existing problems in the clinical practice for older adults with acute clinical conditions.Methods:Using the random number table method, a random number sequence was generated, and the patients admitted to the Department of Geriatrics of Shenzhen Nanshan Hospital due to acute diseases From January 2019 to September 2021 were enrolled in the ACE model intervention group(160 cases)and the control group(77 cases)in a 2: 1 ratio.The inclusion criteria were based on disease severity, frailty assessment, and activity of daily living(ADL)assessment.The intervention time was 1-3 weeks.Outcomes of the patients include ADL, hospitalization days, hospitalization expenses, drug proportion, human resource investments, adverse events, 30-day readmission rate, and 1-year mortality.Results:There were no significant difference in baseline indicators such as frailty index and ADL score between the two groups at admission.The ADL score(Barthel index)of the ACE group was significantly improved compared with the control group at discharge(81.71±14.23 vs.70.9±23.89, P<0.001)and at 30 days after discharge(85.84±15.25 vs.68.29±30.91, P<0.001). The hospital cost[(12 735.81±6 541.41)¥ vs.(16 391.54±12 962.34)¥, P=0.002], drug proportion(21.34% vs.28.93 %, P=0.036)and 30-day readmission rate(13.1% vs.23.4%, P=0.037)of the ACE group were significantly lower compared to the control group.The human resource input(32.97±6.72 vs.25.03±5.31, P=0.008)and patient satisfaction(98.23% vs.90.66%, P=0.031)in the ACE group were significantly higher than those of the control group.(4)The incidence of adverse events during hospitalization was significantly lower in the ACE group than in the control group in terms of aspiration(0.63% vs.20.8%, P<0.001), falls(0 vs.10.4%, P<0.001), incontinence dermatitis(0 vs.3.9%, P=0.033), and 1-year mortality(6.3% vs.24.7%, P<0.001). There was no significant difference in the average length of stay(8.98±4.25 vs.10.03±5.32, P=0.101), pressure sores(13.01±4.77 vs.13.27±4.89, P=0.364), DVT risk score(8.53±2.79 vs.8.89±2.76, P=0.340)and medical staff satisfaction(73% vs.80%, P=0.240)between the two groups. Conclusions:The ACE model helps to reduce the disability rate of elderly patients with frailty, adverse events during hospitalization, save drug costs, and improve patient satisfaction.It is worth promoting in geriatric practice, but its localization management details and processes still face many challenges.
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Objective:To observe the effect of acupuncture in the treatment of accommodative myopia in children.Methods:A total of 76 children with accommodative myopia who met the inclusion criteria were divided into a control group or a test group according to the random number table method,with 38 cases in each group.The control group was given education on eye hygiene,and the test group was treated with acupuncture twice a week for 2 months in addition to the intervention used in the control group.The patient's uncorrected visual acuity(UCVA),refraction,and axial length(AL)were measured before treatment and 1 month and 2 months after treatment.Results:After 1 month of treatment,there was no significant difference in the UCVA between the two groups(P>0.05);after 2 months of treatment,the UCVA of the test group was better than that of the control group(P<0.05).After 1 and 2 months of treatment,the refraction of the two groups was significantly different from that before treatment(P<0.01),but there was no significant difference between the two groups(P>0.05).After 1 and 2 months of treatment,the AL in the control group was increased compared with that before treatment(P<0.05),while there was no significant change in the test group(P>0.05),and there was no significant difference between the two groups(P>0.05).Conclusion:Acupuncture treatment can improve UCVA in children with accommodative myopia.