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Objective To investigate the clinical and pathological features of adenoid basal cell carcinoma(ABC),adenoid cystic carcinoma(ACC),and basaloid squamous cell carcinoma(BSCC)with basaloid charac-teristics and improve the diagnostic and differential diagnostic ability of clinicians and pathologists for these lesions.Methods A retrospective study was conducted on the clinical and pathological data of 4 cases of ABC,1 case of ACC,and 3 cases of BSCC diagnosed and treated at Shenzhen Maternal and Child Health Hospital,Southern Medical University from April 2018 to December 2022.Pathological slides were reviewed and relevant literature was analyzed and summarized.Results All three types of tumors were common in postmenopausal women and were associated with high-risk HPV infection.ABC was a low-grade cancer and patients were often clinically asymp-tomatic.It was usually detected incidentally during cervical screening due to cytological abnormalities,or after cervical cone biopsy or hysterectomy for HSIL.It presented as superficial cervical infiltration and clinical staging was often early.ACC and BSCC were intermediate to high-grade cancers and they often presented with postmenopausal vaginal bleeding.A visible mass was observed on the cervix.The clinical staging was intermediate to advanced.The three types of lesions could coexist.Careful observation of the morphological characteristics and immunohistochemical staining could help with differential diagnosis.None of the 8 patients experienced recurrence or metastasis during follow-up.Conclusion Cervical ABC,ACC and BSCC are rare and they originate from reserve cells.They share the similarities in clinical and pathological morphology,but differ in treatment and prognosis.So,accurate differen-tiation among them has important clinical significance.
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Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE). Material and methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups. Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glycoisogenesis and decreased expressions in platelet activation and complement activation. Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation.
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Cas12a is a programmable nuclease for adaptive immunity against invading nucleic acids in CRISPR-Cas systems. Here, we report the crystal structures of apo Cas12a from Lachnospiraceae bacterium MA2020 (Lb2) and the Lb2Cas12a+crRNA complex, as well as the cryo-EM structure and functional studies of the Lb2Cas12a+crRNA+DNA complex. We demonstrate that apo Lb2Cas12a assumes a unique, elongated conformation, whereas the Lb2Cas12a+crRNA binary complex exhibits a compact conformation that subsequently rearranges to a semi-open conformation in the Lb2Cas12a+crRNA+DNA ternary complex. Notably, in solution, apo Lb2Cas12a is dynamic and can exist in both elongated and compact forms. Residues from Met493 to Leu523 of the WED domain undergo major conformational changes to facilitate the required structural rearrangements. The REC lobe of Lb2Cas12a rotates 103° concomitant with rearrangement of the hinge region close to the WED and RuvC II domains to position the RNA-DNA duplex near the catalytic site. Our findings provide insight into crRNA recognition and the mechanism of target DNA cleavage.
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Sistemas CRISPR-Cas , ARN Guía de Sistemas CRISPR-Cas , División del ADN , ARN/química , ADN/química , Proteínas Bacterianas/metabolismoRESUMEN
Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.
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Objective:To determine the expression of Brahma-related gene 1 (BRG1) in cutaneous squamous cell carcinoma (cSCC) tissues and cells, and to investigate molecular mechanisms underlying the regulatory effect of its interaction with activating transcription factor 2 (ATF2) on the proliferation, migration and invasion of cSCC cells.Methods:From 2015 to 2021, 66 paraffin-embedded actinic keratosis (AK) tissue samples and 80 paraffin-embedded cSCC (including squamous cell carcinoma in situ) tissue samples were collected from the Department of Dermatology, Affiliated Hospital 2 of Nantong University, and the diagnoses of all the cases were confirmed histopathologically; at the same time, 35 paraffin-embedded normal skin tissue samples obtained by cosmetic surgery served as normal control group. Immunohistochemical staining was performed to determine the BRG1 expression in cSCC, AK, and normal skin tissues, and correlations between BRG1 expression and clinicopathological parameters of cSCC patients were analyzed. Fresh tissue samples were collected from 12 cSCC patients and 12 healthy controls, and cSCC cell lines A431 and Scl-1 and a human immortalized keratinocyte cell line HaCaT were routinely cultured; real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to determine the mRNA expression of BRG1 in tissues and cells, and co-immunoprecipitation assay and cellular immunofluorescence staining were conducted to analyze the interaction between BRG1 and ATF2. The expression of BRG1 (BRG1 siRNA1 - 5 groups) and ATF2 (ATF2-shRNA group) in A431 and Scl-1 cells was knocked down by RNA interference, and cells transfected with negative control siRNA or shNC served as controls (control siRNA group and shNC group, respectively), cell counting kit-8 (CCK8) assay, colony formation assay, cell scratch assay, and Transwell assay were conducted to evaluate effects of knocking down BRG1 and ATF2 on the proliferation, migration, and invasion of cSCC cells. Comparisons of measurement data among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were conducted using Dunnett- t test. Results:Immunohistochemical staining showed that the expression intensity of BRG1 protein was significantly lower in the cSCC and AK tissues than in the normal skin tissues ( χ2 = 44.40, P < 0.001). qRT-PCR showed that the mRNA expression level of BRG1 was significantly lower in the cSCC tissues (1.345 ± 0.956) than in the normal skin tissues (2.499 ± 1.501, t = 2.25, P = 0.035), and also significantly lower in A431 and Scl-1 cells (0.041 ± 0.002, 0.026 ± 0.003, respectively) than in HaCaT cells (0.135 ± 0.033, t = 4.95, 5.73, P = 0.008, 0.005, respectively). The low expression of BRG1 was associated with tumors at sun-exposed sites ( P = 0.041), low tumor differentiation ( P = 0.001), and high Broder′s grade ( P < 0.001) in the cSCC patients. In both A431 cells and Scl-1 cells, the BRG1 siRNA1 group and BRG1 siRNA2 group showed significantly increased numbers of cell colonies, migratory cells and invasive cells, as well as cell migration rates compared with the control siRNA group (all P < 0.05). Co-immunoprecipitation assay showed that BRG1 protein could bind to ATF2 protein in A431 and Scl-1 cells, and immunofluorescence staining showed that the two proteins were co-localized; compared with the control siRNA group, the BRG1 siRNA1 group (both A431 and Scl-1 cells) and BRG1 siRNA2 group (A431 cells) both showed increased phosphorylation and activation of ATF2 (all P < 0.05) ; in both A431 cells and Scl-1 cells, the shATF2 group showed significantly decreased numbers of cell colonies (both P = 0.001), cellular proliferative activity at 24 - 96 hours (all P < 0.001), and numbers of migratory cells and invasive cells compared with the shNC group (all P ≤ 0.001) . Conclusion:BRG1 was lowly expressed in the cSCC and AK tissues, and could inhibit the proliferation, migration, and invasion of cSCC cells; ATF2 could promote the proliferation, migration, and invasion of cSCC cells; BRG1 may exert an anti-tumor effect by interacting with ATF2 protein and inhibiting phosphorylation-dependent activation of ATF2.
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@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx(Lfx)-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx(Lfx)-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.
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Background: Globally, several generations of doctors in the field of lymphedema have created numerous publications. To date, no bibliometric analysis has been performed specifically on these publications. For the further promotion of research on lymphedema and to align with the international research frontiers, it is essential to understand the current state of Lymphedema research output. Objective: This study aims to statistically and visually analyze the characteristics of publications output, distribution of contributions and development process of lymphedema, enriching the knowledge base of Lymphedema, and then seek potential research topics and collaborators. Methods: Based on the Web of Science core collection database, we firstly analyzed the quantity and quality of publications in the field of lymphedema, secondly profiled the publishing groups in terms of country, institution, author's publication and cooperation network, and finally sorted out and summarized the hot topics of research. Results: A total of 8569 papers were retrieved from 1900-2021. The top4 journals with the most publications were LYMPHOLOGY, LYMPHATIC RESEARCH AND BIOLOGY, PLASTIC AND RECONSTRUCTIVE SURGERY and ANNALS OF SURGICAL ONCOLOGY. The top 4 countries with the most publications were USA, Japan, UK, and China. The United States dominates the total number of publications and the international cooperation network. The most productive research institution is Harvard University, and the research institution with the most collaborating institutions is Memorial Sloan Kettering Cancer Center. Mortimer, Peter S contributes the most research in this field. The research achievements of Japanese scholars in this field are of great significance. The top 5 ranked keywords are "Breast Cancer", "Health-Related Quality Of Life", "Lymphscintigraphy", "Lymphovenous Anastomosis", and "Lymphangiogenesis". Conclusion: More and more scholars are devoted to the research of cancer-related Lymphedema. It is foreseeable that breast cancer-related lymphedema and lymphangiogenesis will remain a focus of future research. Advances in Lymphatic vessel imaging and the development of lymphatic microsurgery will further play a role in the clinical workup of lymphedema. Meanwhile, This study can help researchers identify potential collaborators and partner institutions and contribute to further research.
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BACKGROUND: This study investigated the impact of coronary angiography on outcomes of emergency operation in acute type A aortic dissection (ATAAD) patients who were initially misdiagnosed as an acute coronary syndrome. METHODS: From October 2016 to April 2019, 129 patients underwent emergency operation for ATAAD in our institution, including 21 patients (16.3%, coronary angiography group) who received preoperative coronary angiography without knowledge of the ATAAD, and the rest 108 did not (Non-coronary angiography group). Preoperative clinical characteristics, 30-day mortality and postoperative complications were compared. Multivariable logistic regression was performed to confirm the independent prognostic factors for short-term and long-term outcomes. RESULTS: Patients undergoing coronary angiography had higher prevalence of preoperative hypotension or shock (61.9% vs 35.2%, P = 0.022), ischemic changes on electrocardiogram (66.7% vs 37.0%, P = 0.012), platelet inhibition (ADP-induced inhibition 92.0% vs 46.0%, P = 0.001), and coronary involvement (66.7% vs 30.6%, P = 0.002). 30-day mortality was 4.8% versus 9.3% (P = 0.84). Coronary angiography group had more intraoperative bleeding (1900 ml vs 1500 ml, P = 0.013) and chest-tube drainage on the first postoperative day (1040 ml vs 595 ml, P = 0.028). However, preoperative coronary angiography was not independent risk factors for 30-day mortality (OR 0.171, 95%CI 0.013-2.174, P = 0.173) and overall survival (HR 0.407; 95%CI 0.080-2.057; P = 0.277). CONCLUSION: Patients undergoing coronary angiography carried a higher risk of preoperative hemodynamic instability, myocardial ischemia, and perioperative bleeding. However, unintentional coronary angiography did not have a significant impact on short-term and long-term outcomes of emergency surgery in ATAAD.
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Disección Aórtica , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Angiografía Coronaria , Puente de Arteria Coronaria/efectos adversos , Humanos , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
IntroductionClinical Trials Units (CTUs) are a key component of delivering non-commercial and commercial clinical research globally. Within the UK, CTUs are seen as a specialist and independent entity available to all researchers requiring support to setup, conduct and deliver clinical trials. Therefore, an involvement of a CTU is highly recommended by national regulators and positively accepted by funders, especially for drug and/or medical device and/or complex intervention trials. AimThis study aims to determine the challenges associated with the management of Covid-19 research managed via the CTU workforce, including the challenges associated with quality assurance, trial setup and data management. Additionally, this study will explore the by-stander effect on trial staff by way of evaluating the mental and physical health impact. Methods/ DesignThis is a mixed methods study. An online novel questionnaire survey study will be conducted among the UK CTU workforce. Quantitative data will be collected using the Qualtrics XM platform. We aim to recruit up to 1,500 CTU staff across the UK workforce. A subgroup sample will be randomly invited to take part in semi-structured interviews. Therefore, this survey will generate both quantitative and qualitative data inclusive of demographic data. ResultsThe findings will inform current initiatives and identify key themes for prioritising in further research to develop robust approaches to support CTU staff, including the development of a start-re-start framework for CTUs for any future pandemics relevant to developing and delivering communicable diseases and non-communicable diseases-based research. Strengths/LimitationsThe validation of the EPIC impact questionnaire used qualitative and quantitative methods which is a strength of the study. However, the study has a single timepoint to obtain data with the secondary outcome measures to be completed at two timepoints as this is an exploratory study attempting to obtain a wider data pool.
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We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 Å from other K+ channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K+ channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state.
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Canal de Potasio Kv1.3/metabolismo , Canal de Potasio Kv1.3/ultraestructura , Secuencia de Aminoácidos/genética , Sitios de Unión/fisiología , Humanos , Activación del Canal Iónico/fisiología , Canal de Potasio Kv1.3/efectos de los fármacos , Potenciales de la Membrana , Microscopía Electrónica/métodos , Modelos Moleculares , Conformación Molecular , Potasio/metabolismo , Canales de Potasio/metabolismo , Canales de Potasio/ultraestructura , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de Potasio con Entrada de Voltaje/ultraestructura , Alineación de Secuencia/métodosRESUMEN
Objective:To investigate the clinical efficacy of induced membrane technique in the staged treatment of adult chronic hematogenous osteomyelitis (CHOM) of long bone.Methods:The clinical data were retrospectively analyzed of the 22 adult patients with CHOM of long bone who had been admitted to the 920th Hospital, Joint Logistics Support Force of PLA from January 2016 to December 2019. There were 18 males and 4 females, aged from 16 to 56 years (average, 31.81 years). Their disease duration ranged from 0.6 to 42.0 years, averaging 18.4 years. By the Cierny-Mader anatomical classification, 4 cases were type Ⅰ, 6 cases Type Ⅲ, and 12 cases type Ⅳ. In the first stage, the bone defects were filled with antibiotic bone cement after thorough debridement. In the second stage when the infection had been controlled, the bone defects were repaired with bone grafts after removal of the bone cement. Bone healing time and complications were followed up. The treatment effects were evaluated by comparisons of the infection control indexes [including clinical manifestations like local redness, swelling, pus, and pain, and blood white blood cell count, C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) as well] before the primary surgery, before the secondary surgery and at the last follow-up.Results:The volumes of the bone defects after stage-one debridement ranged from 54 cm 3 to 176 cm 3 (mean, 90.9 cm 3). All patients were followed up for 20 to 51 months (mean, 30.1 months) after surgery. All bone defects healed after 4 to 11 months (mean, 6.6 months). Postoperatively, infection developed at the bone extraction site of the posterior superior iliac spine in 3 cases and pain was observed at the donor site in one case, but the conditions were relieved after symptomatic treatment. Fracture and plate breakage occurred at the bone defect site in one case who had fallen down 7 months after operation, but responded to reoperation. The last follow-up revealed such symptoms as redness, swelling and pus discharge in none of the patients. The white blood cell count [(5.70 ± 1.57) × 10 9/L and (5.65 ± 1.58) × 10 9/L], CRP [(7.56 ± 2.57) mg/L and (7.25 ± 3.83) mg/L] and ESR [(9.64 ± 2.90) mm/h and (10.55 ± 5.23) mm/h] before the secondary surgery and at the last follow-up were significantly lower than those before the primary surgery [(8.24 ± 2.18) × 10 9/L, (49.54 ± 19.56) mg/L, and (42.68 ± 13.77) mm/h] (all P < 0.05). However, there were no significant differences between the indexes before the secondary surgery and at the last follow-up ( P > 0.05). Conclusion:In the staged treatment of adult CHOM of long bone, the induced membrane technique can effectively control infection, achieve repair of bone defects, and reduce complications.
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Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.
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AIM:To investigate the factors affecting patients with post traumatic infectious endophthalmitis(PTIE)relieving from blindness.METHODS: A retrospective study was conducted on 169 patients(169 eyes)with PTIE from January 2010 to December 2020 in the department of ophthalmology, the Affiliated Hospital of Nantong University. After treatment of intravitreal injection of antibiotics(IVIA)and/or pars plana vitrectomy(PPV), the patients were divided into the getting rid of blindness group(103 eyes)and unilateral blindness group(66 eyes)according to the last follow-up of best correct visual acuity(BCVA)≥0.05. The factors affecting the patients to get rid of blindness were analyzed.RESULTS: The rate of relieving from blindness was 53.5%. Univariate analysis showed that BCVA before treatment ≥ hand movement, no retinal detachment, fundus grade of endophthalmitis < grade 3 and no strong virulence of infected microorganisms were beneficial for patients to get rid of blindness(P<0.05). Multivariate Logistic regression analysis identified that BCVA before treatment ≥ hand movement(OR=0.253, 95%CI: 0.108-0.592)and no retinal detachment(OR=0.241, 95%CI: 0.103-0.564)were favorable factors for patient to get rid of blindness.CONCLUSION: Better BCVA before treatment, no retinal detachment, endophthalmitis fundus grade < 3, and no strong virulence of infected microorganisms are favorable factors for patients with PTIE to get rid of blindness finally.
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OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years (QALYs)as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5%;one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ,durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio (ICER)of 1 467 546.54 yuan/QALY,which was much higher than 3-fold per capita gross domestic products (GDP)in 2020(217 713 yuan)as willingness-to-pay (WTP)threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 (217 713 yuan). CONCLUSIONS From the perspective of Chinese health care system ,there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.
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Groundwater is an important water source in the central Guohe River basin but pollution and water quality deterioration present a significant challenge. Here, 80 groups of groundwater samples were collected between June and September 2019 including 61 groups of shallow groundwater samples, 9 groups of middle groundwater samples, and 10 groups of deep groundwater samples. The hydrochemical characteristics and formation mechanisms of groundwater at these different depths were analyzed using statiatical techniques, Piper triangular diagrams, Gibbs figures, and ion ratios. The following results were noted:â Groundwater is weakly alkaline overall, and the dominant anion and cation at different depths were HCO3- and Na+. The shallow and deep groundwater mainly consist of fresh water while the middle groundwater is mainly brackish water. The hydrochemical typology of the shallow groundwater was mainly HCO3-Ca·Mg and HCO3-Na·Mg. HCO3·SO4·Cl-Na was found to be the dominant hydrochemical typology in the middle and deep groundwater. â¡ The chemical composition of the groundwater shows notable vertical variations. With depth, the mean mass concentrations of TDS, Na+, Mg2+, Cl-, SO42-, and HCO3- first increase and then decreasing, while the mean mass concentration of Ca2+ gradually decreases. These vertical differences are closely related to the sedimentary environment of the aquifer and the intensity of water-rock interaction. ⢠The formation of groundwater hydrochemical characteristics is influenced by water-rock interactions, cation exchange, and human activities, with water-rock interaction dominated by sodium silicate dissolution. Human activities generally have the greatest impact on the shallow groundwater. ⣠The water quality of the deep groundwater is notably better than that of the shallow and middle groundwater. However, excessive exploitation of the deep groundwater resource has led to the formation of a regional groundwater funnel, enhancing the difference in middle and deep groundwater levels. To reduce the risk of ground subsidence and the contamination of the deep water with middle brackish water, deep groundwater exploitation wells should be carefully positioned and regulated.
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As the continuous miniaturization of floating-gate transistors approaches a physical limit, new innovations in device architectures, working principles, and device materials are in high demand. This study demonstrated a nonvolatile memory structure with multilevel data storage that features a van der Waals gate architecture made up of a partially oxidized surface layer/indium selenide (InSe) van der Waals interface. The key functionality of this proof-of-concept device is provided through the generation of charge-trapping sites via an indirect oxygen plasma treatment on the InSe surface layer. In contrast to floating-gate nonvolatile memory, these sites have the ability to retain charge without the help of a gate dielectric. Together with the layered structure, the surface layer with charge-trapping sites facilitates continual electrostatic doping in the underlying InSe layers. The van der Waals gating effect is further supported by trapped charge-induced core-level energy shifts and relative work function variations obtained from operando scanning X-ray photoelectron spectroscopy and Kelvin probe microscopy, respectively. On modulating the amount of electric field-induced trapped electrons by the electrostatic gate potential, eight distinct storage states remained over 3000 s. Moreover, the device exhibits a high current switching ratio of 106 within 11 cycles. The demonstrated characteristics suggest that the engineering of an InSe interface has potential applications for nonvolatile memory.
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A novel highly active fluorescence chemical sensor (TBI) for CN- was synthesized based on triphenylamine-benzothiazole as a new fluorophore, and was used for the first time as a fluorophore for detection of CN- . Fluorescence quantum yield of the probe clearly increased when using triphenylamine-benzothiazole as the group. The probe possessed good selectivity towards CN- and had anti-interference ability over common ions. After adding CN- , the UV-visible spectrum of TBI changed clearly and underwent a dramatic colour change from red to colourless, which could be observed clearly by the naked eye. The limit of detection for CN- was calculated to be 2.62 × 10-8 M, which was well below the WHO cut-off point of 1.9 µM. The novel probe displayed fast sensing of CN- . The detection mechanism was a nucleophilic addition reaction between CN- and a carbon atom -C = N- in indole salt. The π-conjugation and intramolecular charge transfer (ICT) transition in the TBI molecule were destroyed by this addition, which resulted in a change of fluorescence before and after the addition of CN- . The mechanism was verified using theoretical calculation, 1 H NMR titration, and mass spectra. In addition, the probe showed low cytotoxicity and could be used for biological imaging in HeLa cells.
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Cianuros , Colorantes Fluorescentes , Células HeLa , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de FluorescenciaRESUMEN
In this study, eight H9N2 IAVs were isolated from infected diseased, farmed raccoon dogs and arctic foxes. Eight genes shared 98.6%-100% identity among the isolates possessing a PSRSSR/GL motif at the HA cleavage site, which is same as the motif of G1 and Y280 lineages of H9N2 IAVs. The phylogenetic analysis showed that the HA genes of the eight isolates clustered with Y280-like viruses, whereas the NA genes belonged to F/98-like sublineage. Interestingly, the NS, NP, PB2 and PA genes of the isolates were closely related to H7N9 IAVs. This is the first evidence for isolation of H9N2 IAVs from raccoon dogs and arctic foxes. Raccoon dogs and arctic foxes potentially serve as an intermediate host for influenza viruses with pandemic potential toward other animals due to co-expression of both SA α-2,6-Gal and SA α-2,3-Gal receptors in a wide range of their tissues.
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Zorros/virología , Subtipo H9N2 del Virus de la Influenza A/genética , Infecciones por Orthomyxoviridae/veterinaria , Perros Mapache/virología , Animales , China , Femenino , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Masculino , Infecciones por Orthomyxoviridae/virología , FilogeniaRESUMEN
PURPOSE@#Treatment of irreducible femoral intertrochanteric fractures often requires open reduction. However, the technique unavoidably causes patients to suffer greater trauma. As such, minimally invasive techniques should be employed to reduce the surgical-related trauma on these patients and maintain a stable reduction of the fractures. Herein, a minimally invasive wire introducer was designed and used for the treatment of femoral intertrochanteric fractures. The effectiveness of using a wire-guided device to treat irreducible femoral intertrochanteric fractures was evaluated.@*METHODS@#Between 2013 and 2018, patients with femoral intertrochanteric fractures who were initially treated by intramedullary nail fixation but had difficult reduction using the traction beds were retrospectively reviewed. Decision for an additional surgery was based on the displacement of the fracture. The patients were then divided into two groups: those in the control group received an open reduction surgery while those in the observation group received a closed reduction surgery using a minimally invasive wire introducer to guide the wire that could assist in fracture reduction. The operation time, blood loss, visual analogue scale scores, angulation, reduction, neck-shaft angle, re-displacement, limb length discrepancy, and union time were then recorded and analyzed to determine the efficiency of the wire introducer technique. Categorical variables were analyzed by using Chi-square test, while continuous variables by independent t-test and the Mann-Whitney test accordingly.@*RESULTS@#There were 92 patients included in this study: 61 in the control group and 31 in the observation group. There were no significant differences in baseline demographic factors between the two groups. All surgeries were successful with no deaths within the perioperative period. The average follow-up time for the patients was 23.8 months. However, the observation group had a significantly shorter operation time, lower visual analogue scale score, less intraoperative bleeding, and shorter fracture healing time. There were no significant differences in the angulation, reduction, neck-shaft angle, and limb length discrepancy between the two groups.@*CONCLUSION@#The minimally invasive wire guide achieved a similar effect to that of open reduction in the treatment of intertrochanteric fractures with difficult reduction. Moreover, the minimally invasive wire introducer is a good technology that accurately guides the wire during reduction. Indeed, it is an effective technique and achieves good clinical outcomes in restoration of irreducible femoral intertrochanteric fractures.
RESUMEN
Objective:To investigate the efficacy of induced membrane technique combined with anterolateral thigh flap transfer in treating composite foot defect.Methods:A retrospective case series study was performed for 7 patients with composite foot defect treated at 920th Hospital of Joint Logistic Support Force of PLA from February 2014 to December 2018. There were 5 males and 2 females, with the age of 20-73 years [(38.9±16.3)years]. The composite defect located at the forefoot in 5 patients, midfoot in 1, and hindfoot in 1. There were 9 metatarsal bone defects, 1 medial cuneiform bone defect, and 1 calcaneus bone defect. The size of soft tissue defect varied from 6 cm×5 cm to 70 cm×35 cm. At stage I, the anterolateral thigh flap transfer and vancomycin loaded cement implantation were performed. The flap survival and complications were recorded. At stage II, the cement was removed and autogenous bone was grafted into the induced membrane. The duration of two-stage operation, bone union time, and complications were recorded. The postoperative function was assessed using Maryland foot score system before operation and at the last follow-up and postoperative compications were documented.Results:All patients were followed up for 22-54 months [(33.8±9.7)months]. At stage I, flaps survived in all patients, and bulking of the flap was seen in 3 patients. One patient with calcaneus bone defect had repeated infection after operation, and received debridement. At stage II, 6 patients received bone grafting surgery. The duration of two-stage operation was 2-4 months [(2.8±0.9)months]. The bone union time was 3 and 7 months [(4.7±1.2)months]. At the last follow-up, the Maryland foot function score was 63-92 points [(82.1±8.7)points], significantly different from 0 point before operation ( P<0.01). The results were excellent in 1 patient, good in 5, and fair in 1. Except for one nonunion of metatarsal bone, all the other 8 sites were with bone union uneventfully. Conclusion:The induced membrane technique combined with anterolateral thigh flap transfer is an effective protocol for composite foot defect, which can well repair soft tissue and bone defect, and restore walking.