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Streptococcus pyogenes Cas9 (SpCas9) is the most popular tool in gene editing; however, off-target mutagenesis is one of the biggest impediments in its application. In our previous study, we proposed the HH theory, which states that sgRNA/DNA hybrid (hybrid) extrusion-induced enhancement of hydrophobic interactions between the hybrid and REC3/HNH is a key factor in cleavage initiation. Based on the HH theory, we analyzed the interactions between the REC3 domain and hybrid and obtained 8 mutant sites. We designed 8 SpCas9 variants (V1-V8), used digital droplet PCR to assess SpCas9-induced DNA indels in human cells, and developed high-fidelity variants. Thus, the HH theory may be employed to further optimize SpCas9-mediated genome editing systems, and the resultant V3, V6, V7, and V8 SpCas9 variants may be valuable for applications requiring high-precision genome editing.
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Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Edición Génica , Streptococcus pyogenes , Humanos , Edición Génica/métodos , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Streptococcus pyogenes/genética , Streptococcus pyogenes/enzimología , Células HEK293 , Mutación INDEL , ARN Guía de Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas/metabolismo , ADN/genética , ADN/metabolismo , ADN/químicaRESUMEN
The anomalous Hall effect induced by the in-plane magnetic field (anomalous planar Hall effect) has recently attracted a lot of interests due to its numerous advantages. Although several schemes have been put forward in theory, experimental observations in many materials so far are often accompanied by planar Hall effects due to other mechanisms, rather than the pure anomalous planar Hall effect (APHE). We propose the surface state of the strained topological insulator as an ideal candidate to observe this effect. The surface state exhibits a pure APHE, characterized by a linear dependence on the magnetic field and a 2πperiodicity, which remains robust against the scattering of non-magnetic and various magnetic impurities, as long as the uniaxial strain preserves mirror symmetry. Although a general strain that breaks the mirror symmetry can induce the conventional Drude Hall effect, the anomalous contribution remains dominant. Furthermore, we present a feasible scheme to distinguish between the two contributions based on their distinct magnetic field dependencies. Our work is of great significance for promoting experimental observation of the APHE and provides reference value in the search for other realistic materials.
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Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage â ¡-â ¢ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage â ¡ and 186 were stage â ¢. Among stage â ¡ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage â ¢ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage â ¢C (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage â ¡ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage â ¢ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage â ¢ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
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Melanoma , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales/uso terapéutico , Apoptosis , China , Supervivencia sin Enfermedad , Pueblos del Este de Asia , Inmunoterapia , Interferón-alfa/uso terapéutico , Metástasis Linfática , Melanoma/tratamiento farmacológico , Melanoma/patología , Receptor de Muerte Celular Programada 1/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
Objective: To explore the influencing factors of electronic cigarette use among adolescent students in China. Methods: We searched CNKI, Database of Chinese sci-tech periodicals (VIP), Wan-fang database, PubMed, Web of Science and ScienceDirect for potentially relevant articles published from the inception to March 20th, 2023. The Metagen package in R was used for Meta-analysis. Results: A total of 19 publications with a sample size of 5 336 017 were identified. The results showed that electronic cigarette use among Chinese adolescent students was associated with gender (OR=2.41, 95%CI: 2.03-2.86), close friends smoking (OR=3.02, 95%CI: 2.08-4.39), current smoking (OR=11.26, 95%CI: 4.35-29.18), friends using electronic cigarettes (OR=5.19, 95%CI: 2.01-13.38), thinking smoking makes young people look more attractive (OR=2.00, 95%CI: 1.35-2.97), type of school (OR=2.10, 95%CI: 1.59-2.78), thinking smoking makes people feel more comfortable in social situations (OR=3.58, 95%CI: 2.99-4.28), other tobacco use (OR=5.53, 95%CI: 3.33-9.20), and ever experimented with cigarette use (OR=9.32, 95%CI: 4.38-19.80). Conclusion: The influencing factors for electronic cigarette use among adolescent students in China include gender, close friends smoking, current smoking, friends using electronic cigarettes, thinking smoking makes young people look more attractive, type of school, thinking smoking makes people feel more comfortable in social situations, other tobacco use, and ever experimented with cigarette use.
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Sistemas Electrónicos de Liberación de Nicotina , Vapeo , Adolescente , Humanos , Estudios Transversales , Pueblos del Este de Asia , EstudiantesRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of Rotarex catheter system in treating femoropopliteal artery stenosis accompanied with thrombosis. METHODS: From Jun. 2017 to Dec. 2019, the clinical data of 32 femoropopliteal artery stenosis accompanied with thrombosis cases treated with Rotarex catheter system were retrospectively analyzed. There were 23 males and 9 females aged from 50 to 89 years and the mean age was (70.7±10.3) years. Six cases had acute course of disease (≤2 weeks), 17 cases had subacute course of disease (>2 weeks, ≤3 months), and 9 cases had chronic course of disease (>3 months). Mean lesion length was (23.4±13.7) cm, mean occlusion length was (19.9±13.3) cm, and in-stent occlusion 7 cases. The superficial femoral artery (SFA) was involved in 13 cases, the popliteal artery (PA) was involved in 8 cases, and both SFA and PA were involved in the other 11 cases. All the cases were treated with Rotarex catheter system. When necessary, suction with large lumen catheter was enabled. Residual stenosis was treated with percutaneous transluminal angioplasty (PTA). Drug-coated balloon (DCB) was only used in patients with financial status, and stent was used only when it was necessary. Heparin was used for 24 h after procedures, and after that, antiplatelet agents were used. Doppler ultrasonography was taken during the followed-up. RESULTS: Technical success was 100%, and mean procedure time was (107.4±21.5) min. 8F (1F≈0.33 mm) and 6F Rotarex catheter were used in 27 and 5 cases respectively. In 27 cases, forward flow was obtained immediately after debulking with Rotarex catheter, and in the other 5 cases, suction with large lumen catheters were used. PTA was used in all 32 cases. DCB were used in 8 cases, of which 4 were used in in-stent stenosis. Twelve cases were implanted stents. There were no perioperative deaths. The only one procedure related complication was distal embolism. We took out the thrombus with guiding catheter. In all cases, mean hospital stay were (4.6±1.5) d. The ankle brachial index increased from 0.32±0.15 to 0.86±0.10 after treatment (t=-16.847, P < 0.001). The Rutherford stages decreased significantly (Z=-4.518, P < 0.001). All the patients were followed up for 6.0-36.0 months, and the median time was 16.0 months. 2 cases stopped antiplatelet agents, which resulted in acute thrombosis. Another percutaneous mechanical thrombectomy and PTA were taken in one of them. Two cases died of cardiovascular disease during the follow-up, and no amputation was observed. Target lesion restenosis occurred in 7 cases during the follow-up, and target lesion revascularization (TLR) was taken in two of them. CONCLUSION: In treating femoropopliteal artery stenosis accompanied with thrombosis, Rotarex catheter can remove thrombus effectively, and that can expose underlying lesions and reduce stent use and complications rates. It is a safe and effective method.
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Arteria Femoral , Trombosis , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Arteria Femoral/cirugía , Estudios Retrospectivos , Constricción Patológica , Inhibidores de Agregación Plaquetaria , Resultado del Tratamiento , CatéteresRESUMEN
A 2π-periodic anisotropic magnetoresistance (AMR) violating the classical two-fold symmetry is found in the multi-Weyl semimetals. It is induced by the intrinsic magnetization due to the magnetic doping. The monopole charge influences the novel AMR, strongly. For single- and triple-Weyl semimetals, tilt along thex-direction or equivalently along they-direction is indispensable in the nonzero AMR. However, the AMR with 2πperiod even exists for the untilted double-Weyl case. The oscillation of the conductivity for the triple one is out-of-phase compared to the other two. We decompose the conductivity into theπand 2πparts. The amplitude of the dominant 2πcontribution increases almost linearly with the magnetization for all three cases. Moreover, the strength of the magnetic scattering strongly affects the magnitudes. Our work will contribute to a deeper understanding of the AMR in multi-Weyl semimetals.
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Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (Pnon-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q2 subgroup of mtDNAcn, those in the Q1 subgroup (HR=2.00,95%CI:1.08-3.70) and Q4 subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q3 subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (Pinteraction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.
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ADN Mitocondrial , Neoplasias Hepáticas , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Femenino , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/genética , Masculino , MitocondriasRESUMEN
Objectie To investigate the susceptibility of drug-resistant staphylococci isolated from different parts of the anterior segment to levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin. Methods: Experimental Study. A total of 67 patients with anterior segment infection (33 cases of conjunctivitis, 6 cases of bacterial keratitis, 7 cases of blepharitis, 9 cases of neonatal dacryocystitis, 9 cases of neonatal dacryocystitis, 1 case of adult dacryocystitis and 11 cases of other infectious eye diseases) were collected from the conjunctival sac, cornea, eyelid margin and lacrimal sac. Minimum inhibitory concentration (MIC) determination of methicillin-resistant Staphylococcus (MRS) strains and ß-lactamase-producing (ß-Lac) strains by a micro-liquid-based method, according to the M100 standard of the American Institute for Clinical and Laboratory Standardization Susceptibility and resistance determinations were made. Data were statistically analyzed using Chi-square or Fisher's exact test. Results: Thirty-five MRS, 30 ß-Lac and 2 ß-Lac MRS isolates were identified from 67 multidrug-resistant Staphylococcus . There were 3, 9, 4, and 19 MRS isolates isolated from the lacrimal sac, cornea, eyelid margin and conjunctival sac, accounting for 3/4, 9/12, 4/8, 19/43 (44.2%) of the isolated sites respectively. There were 1, 3, 3, and 23 ß-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of ß-Lac isolates isolated from patients with a diagnosis of conjunctivitis was 17 (25.3%) from the conjunctival sac. Among the MRS strains isolated from the cornea and lacrimal sac, 5 (7.5%) and 3 (4.5%) were from patients diagnosed with bacterial keratitis and neonatal tear, respectively. The number of MRS strains and ß-Lac isolates isolated from patients with a diagnosis of blepharitis were both 3 (4.5%) from the lid margin.Among the strains isolated from the eyelid margin and the conjunctival sac, drug-resistant Staphylococcus epidermidis was the main strain, the drug-resistant Staphylococcus aureus was the major isolates in lacrimal sac and cornea. Among the 35 MRS isoaltes, 25, 24, 12, 12, and 11 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, clindamycin and tobramycin, and the sensitivity rates were 71.4%, 68.6%, 34.3%, 34.3% and 31.4%, the difference was statistically significant (χ2=22.756, P<0.001), The sensitivity rates of levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin against MRS isolates from the anterior segment were both statistically significant differences (χ2=18.493, 11.594, 8.906, 9.841, 16.059; all P<0.05). The susceptibility rates of MRS isolates against five antibiotics was statistically significant differences (χ2=33.080, P<0.001). Among the 30 ß-Lac isolates, 27, 22, 19, 16, and 8 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, tobramycin and clindamycin, and the sensitivity rates were 90.0 % , 73.3%, 63.3%, 53.3% and 26.7%, the difference was statistically significant (χ2=28.280, P<0.001). The sensitivity rates of five antibiotics against ß-Lac isolates from the anterior segment were both statistically significant differences (χ2=50.971, 24.543, 48.147, 44.899, 18.676; all P<0.001). The susceptibility rates of ß-Lac isolates against five antibiotics was statistically significant differences (χ2=23.383, P<0.001). The sensitivity of cefazolin sodium and fusidic acid against ß-Lac isolates were higher than MRS isolates. Conclusions: Cefazolin sodium and fusidic acid may be the best choice for the treatment of drug-resistant Staphylococcus isolated from anterior conjunctival sac, cornea, eyelid margin and lacrimal sac, especially for ß-Lac-producing drug-resistant Staphylococcus infection.
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Blefaritis , Conjuntivitis , Dacriocistitis , Queratitis , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Adulto , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cefazolina/farmacología , Cefazolina/uso terapéutico , Clindamicina/uso terapéutico , Dacriocistitis/tratamiento farmacológico , Ácido Fusídico/farmacología , Ácido Fusídico/uso terapéutico , Humanos , Recién Nacido , Queratitis/microbiología , Levofloxacino/farmacología , Levofloxacino/uso terapéutico , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus , Tobramicina/farmacologíaRESUMEN
Objective: To explore the association between self-reported gingival bleeding and prevalent hypertension among adults in Zhejiang with a cross-sectional study. Methods: After excluding participants with self-reported, physician-diagnosed heart diseases, stroke, diabetes, cancer, and those who never or rarely brush their teeth at baseline study, 48 625 participants aged 30-79 in the China Kadoorie Biobank (CKB) study from Tongxiang, Zhejiang were included for the final analysis. Three multivariable logistic regression models were used to estimate the odds ratios (ORs) for the associations of self-reported gingival bleeding with prevalent hypertension. Results: The mean age of women was (51.2±9.2) years, and 42.9% of participants had prevalent hypertension. The percentage of self-reported frequent gingival bleeding was 6.56% (95%CI: 6.38%-6.75%), significantly higher among women (8.08%, 95%CI: 7.82%-8.35%) than among men (4.36%, 95%CI: 4.12%-4.60%) (P<0.001). After adjusting for socio-demographic factors, behavioral lifestyle, sleep duration, BMI, waist circumference, snoring, in comparison with men whose gingivae never or rarely bleed while brushing teeth, the odds ratio (95%CI) of hypertension for those with occasional, and frequent gingival bleeding were 1.04 (0.96-1.12) and 1.18 (1.02-1.37), respectively (trend P =0.038). The corresponding figures for women were 0.96 (0.91-1.02) and 0.95 (0.86-1.05), respectively (trend P=0.344). Conclusion: Frequent gingival bleeding was positively associated with prevalent hypertension among men.
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Hipertensión , Adulto , China/epidemiología , Estudios Transversales , Femenino , Hemorragia Gingival , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , AutoinformeRESUMEN
Objective: To evaluate the effect of mechanical debulking in treating arteriosclerosis occlusive disease of lower extremity. Methods: The clinical data of 52 arteriosclerosis occlusive disease of lower extremity cases treated with Rotarex mechanical debulking system from June 2017 to June 2020 at Department of Intervention Vascular Surgery,Peking University Third Hospital were retrospectively analyzed. There were 37 males and 15 females,aged(69.4±10.1)years(range:47 to 89 years).Lesion length was (21.6±12.9)cm(range:4 to 45 cm),occlusion length was (18.5±11.8)cm(range:4 to 45 cm).The lesion was located in iliac artery(IA) in 6 cases,femoral-popliteal artery(FPA) in 42 cases,and both IA and FPA in 4 cases. All the cases were treated with Rotarex mechanical debulking system. Residual stenosis more than 50% were treated with percutaneous transluminal angioplasty(PTA).Drug coated balloon was used in part of them,and stent was used only when it was necessary. The patient's operation, complications, postoperative target vessel restenosis and reoperation were collected. The paired sample t test and rank sum test was used for data comparison and the postoperative target vessel patency rate was analyzed by Kaplan-Meier survival curve. Results: All the 52 cases obtained technical success. Percutaneous transluminal angioplasty was used in all cases,and drug coated balloon were used in 11 cases. Twenty-six stents were implanted in 24 cases (2 cases implanted 2 stents).Nine stents were implanted in IA and 15 in FPA. The length of stents was (11.3±3.3)cm(range:6 to 23 cm).There were 3 procedure related complications: one of them was acute occlusion in an iliac lesion,and thrombectomy was applied urgently,and the result was good. And the other two were distal embolism. The thrombus were took out with guiding catheter. The hospital stay was (4.8±1.9)days. The ankle brachial index increased from 0.34±0.16 to 0.81±0.16 after treatment(t=-25.160,P<0.01).The Rutherford stages decreased from (M(IQR)) 3(1) to 1(1(Z=-6.825,P<0.01).The median followed up time was 19 months(range:6 to 42 months).Two cases stopped antiplatelet agents during follow-up and which result in acute thrombosis 2 weeks and 2 months later respectively. One of them was treated with percutaneous mechanical thrombectomy and the other one was not for gastrointestinal hemorrhage. Four cases died during follow-up,one case died of lung cancer,one died of abdominal infection,and the other 2 cases died of cardiovascular disease,and no amputation was observed. Target lesion restenosis(TLR) more than 50% occurred in 13 cases during the follow-up. All TLR were observed in FPA,and target lesion revascularization was taken in 3 of them. According to Kaplan-Meier survival curve analysis,half-year,1-year and 2-year cumulative patency rates of target vessels in this group was 94.2%,87.4% and 51.4%, respectively. And half-year and 1-year cumulative patency rates just in FPA cases was 92.9% and 84.3%, respectively. Conclusions: Percutaneous mechanical debulking using Rotarex catheter combining PTA can reduce the use of stents in femoral-popliteal artery. It is safe and effective in treating with arteriosclerosis obliterans of lower extremity.
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Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-â , PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-â expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-â expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/patología , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Humanos , Inflamación/patología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico , Microambiente Tumoral , Neoplasias PancreáticasRESUMEN
The article "MiR-1275 promotes non-small cell lung cancer cell proliferation and metastasis by regulating LZTS3 expression, by J. He, L. Yu, C.-M. Wang, X.-F. Zhou, published in Eur Rev Med Pharmacol Sci 2018; 22 (9): 2680-2687-DOI: 10.26355/eurrev_201805_14964-PMID: 29771419" has been retracted by the authors due to a serious ethical concern. The authors state that during an ethics investigation, the ethical approval date (June 2018) of the paper was released after the paper was published. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14964.
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Objective: To investigate the characteristics of slow wave activity (SWA) during sleep and the changes of SWA after adenotonsillectomy in children with severe obstructive sleep apnea (OSA). Methods: A total of 24 children with severe OSA, who completed adenotonsillectomy in Sleep Center of Beijing Children's Hospital and 26 control children category matched for age and sex and excluded from OSA were included as subjects from May 2018 to December 2019. The subjects underwent overnight PSG, as well as SWA analysis of sleep electroencephalogram. The differences of PSG indexes and SWA intensity between children with severe OSA and control children, before and after operation in severe OSA children were compared and the correlations between SWA intensity and PSG indexes were analyzed. Results: The age of the children with severe OSA before surgery was (6.1±1.7) years, including 20 males (83.3%), and the interval M(Q1,Q3) between surgery and follow-up was 6.3 (5.8, 7.1) months. The age of the control children was (6.2±1.1) years, including 20 males (76.9%). In severe OSA group, the M (Q1,Q3) of non-rem sleep stage 1 to total sleep time, obstructive apnea hypopnea index, oxygen desaturation index (ODI) and proportion of oxygen saturation (SpO2)<90% during night sleep to total sleep time were 6.8% (5.6%, 8.9%), 1.2 (0.4, 2.4) events/h, 2.1 (0.7, 4.3) events/h and 0(0, 0) after surgery, respectively, which were lower than those before surgery [9.1% (7.5%, 16.8%), 21.6 (14.1, 39.5) events/h, 23.1 (10.2, 36.0) events/h and 0.8% (0, 3.9%), respectively], while non-rem sleep stage 3 to total sleep time%, rem sleep stage to total sleep time% and lowest SpO2 were (24.3±5.7)%, (19.1±3.7)% and 91%(86%, 94%) after surgery, which were higher than those before operation [(19.0±5.3)%, (15.4±3.9)% and 83%(70%, 88%) respectively] (all P values<0.05). The repeated measure ANOVA of SWA intensity in phase N1 showed no interaction between OSA and sleep time course (F=0.02, P=0.997), the main effect of OSA was statistically significant (F=5.12, P=0.040), SWA intensity in children with severe OSA at stage N1 was higher than that of the control group [SWA(severe OSA group before surgery-control group)(95%CI): 0.379,(0.020, 0.739)], while the main effect of sleep time course was not statistically significant (F=1.66, P=0.191). There was no interaction between adenotonsillectomy and sleep time course (F=0.88,P=0.461), the main effect of surgery was statistically significant (F=8.95, P=0.010), SWA intensity of children with severe OSA at N1 stage after surgery was lower than before [SWA(after surgery-before surgery)(95%CI):-0.572(-0.982, -0.162)] and the main effect of sleep time course was statistically significant (F=6.33, P=0.001). The intensity of SWA in the fourth sleep cycle of N1 stage was positively correlated with ODI (r=0.299, P=0.048). Conclusion: The intensity of slow-wave activity at N1 stage is affected by OSA which might be caused by intermittent hypoxia, and adenotonsillectomy significantly reduces SWA intensity at stage N1.
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Apnea Obstructiva del Sueño , Tonsilectomía , Adenoidectomía , Niño , Preescolar , Electroencefalografía , Humanos , Masculino , SueñoRESUMEN
Objective: To explore the effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion injury in mice. Methods: One hundred 10-Week-old healthy KM mice of SPF grade, weighing 25-28 g, were divided into 5 groups by the random number table method: sham group, focal cerebral ischemia group (I/R group), intermittent fasting group (IF group), metformin group (Met group), metformin+intermittent fasting group (Met+IF group). In IF group, food was provided ad libitum from 8â¶00 to 16â¶00 daily, but the mice were fasted for the rest of the time. In Met group, the mice underwent intraperitoneal injection of metformin (10 mg/kg). In Met+IF group, the mice received the same eating method as the IF group and the same method of metformin injection as Met Group. In Sham group, I/R group and IF group, the mice were intraperitoneally injected with equal volume of normal saline. Mice in all groups were not restricted to drinking water. Random plasma glucose and body weight changes in mice during preconditioning were monitored, and a focal cerebral ischemia-reperfusion model was established 14 days later. The cerebral infarction volume was measured after 1 hour of ischemia and 24 hours of reperfusion. The brain tissues of mice were subjected to Western blot to detect the contents of endoplasmic reticulum stress-related proteins, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and apoptosis proteins (Caspase-3 and Cleaved-caspase 3). Results: After different interventions, there was no significant difference in random plasma glucose changes among the four groups (all P<0.05). The blood glucose level of the mice in the Met+IF group was lower than the sham group, I/R group, IF group and Met group (all P<0.05). GRP78/ß-actin in sham group, I/R group, IF group, Met group, IF+Met group were 0.48±0.05, 1.35±0.10, 0.94±0.05, 0.70±0.14, 0.41±0.37, respectively; CHOP/ß-actin were 0.27±0.04, 1.03±0.03, 0.72±0.04, 0.63±0.04, 0.44±0.01, respectively; Caspase-3/ß-actin were 0.51±0.04, 1.04±0.04, 0.83±0.03, 0.76±0.03, 0.63±0.05, respectively; Cleaved-Caspase-3/ß-actin were 0.17±0.06, 1.01±0.20, 0.75±0.06, 0.51±0.12, 0.29±0.08, respectively, with statistically significant differences (all P<0.001). The counts of GRP78-positive cells in the hippocampus immunohistochemistry in the sham group, I/R group, IF group, Met group, and IF+Met group were 53±5, 192±11, 162±12, 140±10, 114±13, respectively, while the counts of CHOP-positive cells were 35±4, 177±12, 120±12, 100±7, 69±10, respectively, with statistically significant differences (all P<0.001). The relative volume of cerebral infarction in I/R group, IF group, Met group and IF+Met group were 0, 0.333±0.046, 0.258±0.023, 0.116±0.039, 0.111±0.039, respectively, and there were statistically significant differences (all P<0.001). Conclusion: Both Metformin and intermittent fasting can alleviate endoplasmic reticulum stress after cerebral ischemia and reperfusion in mice, and the combination of the two has a better effect.
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Isquemia Encefálica , Metformina , Animales , Apoptosis , Infarto Cerebral , Estrés del Retículo Endoplásmico , Ayuno , Metformina/farmacología , Ratones , ReperfusiónRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of Rotarex mechanical thrombectomy system in treating acute lower limb ischemia. METHODS: From December 2017 to December 2019, the clinical data of 23 acute lower limb ischemia cases treated with Rotarex mechanical thrombectomy system were retrospectively analyzed. There were 14 males and 9 females from 53- to 84-year-old patients and the mean age was (69.1±9.1) years. Duration of symptoms was 6 hours to 14 days (median time 7 days). In the study, 8 acute thromboembolism cases and 15 acute thrombosis cases were included (In which, there was one thromboangiitis obliterans case and two in-stent restenosis cases). In 5 cases, the lesions were located above the groin; in 16 cases, the lesions were located below the groin, and in the other 2 cases, the lesions were located both above and below the groin. All the cases were treated with Rotarex mechanical thrombectomy system. When residual stenosis was greater than 50%, percutaneous transluminal angioplasty (PTA) was used, and stent was used only when it was necessary. Heparin was used 24 h after the procedure, and after that, antiplatelet agents were used in acute thrombosis cases, and oral anti-coagulants were used in acute thromboembolism cases. Doppler ultrasonography was taken during the follow-up. RESULTS: In all the 23 cases, there were 22 successful cases and 1 unsuccessful case, the mean procedure time was (68.2±15.6) min. Percutaneous transluminal angioplasty was used in 18 cases, 7 of which were implanted stents (3 stents were implanted in iliac artery and 4 in superficial femoral artery). There were 3 procedure related complications. The first one was arterial wall injury which resulted in contrast medium extravazation, and in this case, we solved it with prolonged balloon inflation. The second one was distal embolism. We took out the thrombus with guiding catheter. The last one was acute occlusion in a stent, and thrombectomy was applied urgently, and the result was good. Mean hospital stay were (3.6±1.7) days. The ankle brachial index (ABI) increased from 0.25±0.10 to 0.85±0.16 after treatment (t=12.901, P < 0.001). All the patients were followed up for 4.0-28.0 months, and the median time was 12.0 months. One patient stopped antiplatelet agents, which resulted in acute thrombosis 2 months later. Another percutaneous mechanical thrombectomy and PTA were taken. In the failed case, the patient suffered amputation above the knee 3 months later and in another case, the patient died of heart failure 8 months after the procedure. Two target lesion restenosis occurred during the follow-up. Because the patients' symptom was not sever, no procedure was taken. CONCLUSION: Percutaneous mechanical thrombectomy using Rotarex catheter is safe and effective in treating acute lower limb ischemia. For one side, it can restore blood flow to the affected limbs quickly, and for the other, it has the characteristics of minimally invasive and good repeatability. So it should be considered that this me-thod can be widely used for acute lower limb ischemia.
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Isquemia , Trombectomía , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We investigate the linear optical conductivities of the newly-discovered triple-component semimetals. Due to the exactly flat band, the optical conductivity relates to the transition between the zero band and the conduction band directly reflecting the band structure of the conduction electrons in contrast to the other materials. For the low-energy models with various monopole charges, the diagonal conductivities show strong anisotropy. Theω-dependence of interband conductivities for a general low-energy model is deduced. The real part of the interbandσxxalways linearly depends on the optical frequency, while the one ofσzzis proportional toω2/n-1. This can be a unique fingerprint of the monopole charge. For the lattice models, there also exists the optical anomalous Hall conductivity, where a sign change may appear. The characteristic frequencies of the kink structures are calculated, strictly. Our work will help us to establish the basic picture of linear optical response in topological triple-component semimetals and identify them from other materials.
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The nonlinear Hall effect is an unconventional response, in which a voltage can be driven by two perpendicular currents in the Hall-bar measurement. Unprecedented in the family of the Hall effects, it can survive time-reversal symmetry but is sensitive to the breaking of discrete and crystal symmetries. It is a quantum transport phenomenon that has deep connection with the Berry curvature. However, a full quantum description is still absent. Here we construct a quantum theory of the nonlinear Hall effect by using the diagrammatic technique. Quite different from nonlinear optics, nearly all the diagrams account for the disorder effects, which play decisive role in the electronic transport. After including the disorder contributions in terms of the Feynman diagrams, the total nonlinear Hall conductivity is enhanced but its sign remains unchanged for the 2D tilted Dirac model, compared to the one with only the Berry curvature contribution. We discuss the symmetry of the nonlinear conductivity tensor and predict a pure disorder-induced nonlinear Hall effect for point groups C3, C3h, C3v, D3h, D3 in 2D, and T, Td, C3h, D3h in 3D. This work will be helpful for explorations of the topological physics beyond the linear regime.
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Recently, higher-order topological matter and 3D quantum Hall effects have attracted a great amount of attention. The Fermi-arc mechanism of the 3D quantum Hall effect proposed to exist in Weyl semimetals is characterized by the one-sided hinge states, which do not exist in all the previous quantum Hall systems, and more importantly, pose a realistic example of the higher-order topological matter. The experimental effort so far is in the Dirac semimetal Cd_{3}As_{2}, where, however, time-reversal symmetry leads to hinge states on both sides of the top and bottom surfaces, instead of the aspired one-sided hinge states. We propose that under a tilted magnetic field, the hinge states in Cd_{3}As_{2}-like Dirac semimetals can be one sided, highly tunable by field direction and Fermi energy, and robust against weak disorder. Furthermore, we propose a scanning tunneling Hall measurement to detect the one-sided hinge states. Our results will be insightful for exploring not only the quantum Hall effects beyond two dimensions, but also other higher-order topological insulators in the future.
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OBJECTIVE: To evaluate the role of Rotarex mechanical thrombectomy system in treating instent restenosis of peripheral artery disease (PAD). METHODS: The clinical data of 7 in-stent restenosis (ISR) cases of lower extremity PAD from June 2017 to Dec 2018 were retrospectively analyzed. There were 5 males and 2 females and the mean age was (70.0±7.6) years from 59.0 to 76.0 years. All the cases were treated by Rotarex mechanical thrombectomy system. In the 7 cases, time interval from the previous stent implantation to ischemia recurrence was 1.0 to 72.0 months, and the median time was 6.0 months. The period from ischemia recurrence to endovascular therapy was 3 days to 2 years, and the median time was 62 days. Rotarex mechanical debulking catheter and percutaneous transluminal angioplasty (PTA) were used in all the cases, and the stent was used only when it was necessary. Anticoagulation was used for 24 hours after procedures and then antiplatelet agents were used as usual. Doppler ultrasonography was taken during the followed-up. RESULTS: All the 7 cases were successful in technology, 3 of which were implanted with new stents for the fracture of the old ones. while for the other four cases, no new stent was implanted. The ankle-brachial index (ABI) increased from 0.31±0.08 to 0.86±0.08 after treatment (t=-12.84, P < 0.001). Thrombectomy was applied urgently in one case because of acute thrombosis in the stent, and the result was good. There was no other complications in hospital. All the patients were followed up for 5.0-22.0 months, and the median time was 14.0 months. No death and amputation occurred during the follow-up. One patient stopped antiplatelet agents because of gastrointestinal bleeding, which resulted in acute thrombosis. in-stent restenosis reappeared in 3 cases. CONCLUSION: Debulking using Rotarex catheter is safe and effective in treating in-stent restenosis of PAD, especially in reducing stents implantation, but is not good at dealing with old thrombus and proliferating intima, and can do nothing about fractured stents and hyperplasia of intima, so it needs to be combined with stents and drug coated balloons.