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Ultrasound genomics related mitochondrial gene signature for prognosis and neoadjuvant chemotherapy resistance in triple negative breast cancer
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作者 HUAFANG HUANG GUILIN WANG +6 位作者 DONGYUN ZENG LUZ ANGELA TORRES-DE LA ROCHE RUI ZHUO RUDY LEON DE WILDE WANWAN WANG ULF D.KAHLERT WENJIE SHI 《Oncology Research》 2025年第3期631-640,共10页
Background:Neoadjuvant chemotherapy(NAC)significantly enhances clinical outcomes in patients with triple-negative breast cancer(TNBC);however,chemoresistance frequently results in treatment failure.Consequently,unders... Background:Neoadjuvant chemotherapy(NAC)significantly enhances clinical outcomes in patients with triple-negative breast cancer(TNBC);however,chemoresistance frequently results in treatment failure.Consequently,understanding the mechanisms underlying resistance and accurately predicting this phenomenon are crucial for improving treatment efficacy.Methods:Ultrasound images from 62 patients,taken before and after neoadjuvant therapy,were collected.Mitochondrial-related genes were extracted from a public database.Ultrasound features associated with NAC resistance were identified and correlated with significant mitochondrial-related genes.Subsequently,a prognostic model was developed and evaluated using the GSE58812 dataset.We also assessed this model alongside clinical factors and its ability to predict immunotherapy response.Results:A total of 32 significant differentially expressed genes in TNBC across three groups indicated a strong correlation with ultrasound features.Univariate and multivariate Cox regression analyses identified six genes as independent risk factors for TNBC prognosis.Based on these six mitochondrial-related genes,we constructed a TNBC prognostic model.The model’s risk scores indicated that high-risk patients generally have a poorer prognosis compared to low-risk patients,with the model demonstrating high predictive performance(p=0.002,AUC=0.745).This conclusion was further supported in the test set(p=0.026,AUC=0.718).Additionally,we found that high-risk patients exhibited more advanced tumor characteristics,while low-risk patients were more sensitive to common chemotherapy drugs and immunotherapy.The signature-related genes also predicted immunotherapy response with a high accuracy of 0.765.Conclusion:We identified resistance-related features from ultrasound images and integrated them with genomic data,enabling effective risk stratification of patients and prediction of the efficacy of neoadjuvant chemotherapy and immunotherapy in patients with TNBC. 展开更多
关键词 Ultrasound genomics MITOCHONDRIAL Breast cancer NEOADJUVANT Resistance
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DCCD对植物乳杆菌H^+-ATPase活性及基因表达水平的影响
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作者 谢东芳 张祥 +5 位作者 花雨娇 杨俊兴 JIANG Ping 吕常江 方卉 黄俊 《工业微生物》 CAS 2018年第1期8-13,共6页
研究添加外源抑制剂双环己基碳二亚胺(DCCD)对植物乳杆菌H^+-ATPase基因表达水平及酶活力的影响,探讨植物乳杆菌H^+-ATPase的调控机制。分别测定加入DCCD前后的亲本菌和低H^+-ATPase活力突变菌的生长能力、葡萄糖代谢速率、乳酸产量和H^... 研究添加外源抑制剂双环己基碳二亚胺(DCCD)对植物乳杆菌H^+-ATPase基因表达水平及酶活力的影响,探讨植物乳杆菌H^+-ATPase的调控机制。分别测定加入DCCD前后的亲本菌和低H^+-ATPase活力突变菌的生长能力、葡萄糖代谢速率、乳酸产量和H^+-ATPase活性,并通过荧光定量PCR对编码H^+-ATPase的相关基因进行相对定量分析。结果表明,亲本菌ZUST、突变菌ZUST-1和ZUST-2在添加DCCD后菌体生长能力均减弱,葡萄糖代谢速率减慢,乳酸产量降低,H^+-ATPase酶活性也降低。由于受到发酵液中酸性环境以及外源抑制剂DCCD的胁迫,亲本菌ZUST和突变菌ZUST-2编码H^+-ATPase的所有基因在稳定期表达水平都高于对数期。与未添加DCCD相比,添加DCCD的亲本菌和突变菌ZUST-2在对数期H^+-ATPase各基因的表达水平均下调或基本不变,抑制了H^+-ATPase活力从而导致菌株的生长代谢速率减弱。此研究结果为进一步揭示植物乳杆菌中H^+-ATPase在酸胁迫下的调控机制奠定了基础。 展开更多
关键词 植物乳杆菌 H+-ATPase DCCD 荧光定量PCR
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Bias-Variation Dilemma Challenges Clinical Trials: Inherent Limitations of Randomized Controlled Trials and Meta-Analyses Comparing Hernia Therapies
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作者 U. Klinge Andreas Koch +3 位作者 D. Weyhe Enrico Nicolo R. Bendavid Anette Fiebeler 《International Journal of Clinical Medicine》 2014年第13期778-789,共12页
Purpose:Evaluation of hernia therapies according to the current rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses. RCTs have been accepted as a most important tool to confirm a sup... Purpose:Evaluation of hernia therapies according to the current rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses. RCTs have been accepted as a most important tool to confirm a superior effect of an intervention. Unfortunately, in hernia surgery, comparisons of RCTs and correspondingly their use in meta-analyses, are not, surprisingly often, able to confirm any significant impact of a specific procedure due to intrinsic restrictions in a multi-causal setting with its web of influences. Methods:Based on our own experiences of clinical studies in surgery, the present article outlines several situations, with their respective reasons, which argue the severe limitations of RCTs and meta-analysis to define an optimum treatment. Results:Meta-analyses accumulate the variations of each trial, which then may cover any clear causal relationship. RCTs usually are dealing with subgroups of standard patients thus excluding the majority of our patients. Low statistical power of current cohort sizes restricts the analysis of subgroups or of effects with low incidences. Simple comparisons of means frequently are hampered by nonlinear relationships to outcome. The relevance of a specific variable is difficult to separate from other influences. The limited surveillance period of studies ignores a delayed change in outcome. Randomization cannot guarantee a standardized patient’s condition. All the arguments have to be considered as a crucial and fundamental consequence of the bias-variance dilemma or principle of uncertainty in medicine, and underline the many limitations of RCTs to evaluate any specific impact of hernia therapies on e.g. infection, pain or recurrence. Conclusions: Many surgical issues cannot be and should not be investigated by RCTs, in particular, if a marked patients’ heterogeneity has to be considered or the low incidences of the outcome readout cannot be addressed with sufficient statistical power without getting lost in the variation mire. Registries with their non-restricted data-acquisition should be regarded as reliable alternatives for postoperative outcome quality surveillance studies. 展开更多
关键词 Randomized Controlled Trial HERNIA Surgery REGISTRY Meta-Analysis Clinical Study
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Evaluation of the Impact of Laparoscopic Supracervical Hysterectomy for the Treatment of Adenomyosis on Pain Intensity and Patient Satisfaction
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作者 Garri Tchartchian Harald Krentel +1 位作者 Bernd Bojahr Rudy L. De Wilde 《Surgical Science》 2018年第12期509-518,共10页
Objectives. Common symptoms of adenomyosis include pain and bleeding disorders and can severely impact a patient’s quality of life. Few studies report on the impact of hysteroscopy procedures on improving these sympt... Objectives. Common symptoms of adenomyosis include pain and bleeding disorders and can severely impact a patient’s quality of life. Few studies report on the impact of hysteroscopy procedures on improving these symptoms. This study evaluates the effect of laparoscopic supracervical hysterectomy (LASH) in adenomyosis patients on pain in general, pain during intercourse, bleeding disorders and general satisfactoriness of the procedure. Methods. This prospective observational single-arm, single-center study included 256 patients treated with LASH and whose histological analysis revealed adenomyosis. Other inclusion criteria were completed family planning and no more symptom relief with conservative therapy. They completed questionnaires before and after the procedure which evaluated pain in general, pain during intercourse, bleeding disorders and general satisfactoriness of the procedure. Results. Our results showed a significant (p Conclusion. As a minimal invasive procedure associated with low major complication rates, LASH is a qualified therapeutic choice to treat pain and bleeding disorders in adenomyosis patients with completed family planning and in where conservative therapy failed. 展开更多
关键词 HYSTERECTOMY LAPAROSCOPY ENDOMETRIOSIS ADENOMYOSIS LASH PAIN Management
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The new Surgical Instrument in Peritoneal Endometriosis Resection
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作者 Garri Tchartchian Andreas Hackethal +1 位作者 Bernd Bojahr Rudy Leon De Wilde 《Surgical Science》 2012年第8期403-405,共3页
Purpose: Peritoneal resection for the therapy of oncological diseases as well as endometriosis is associated with major problems as injury to neighboring organs and difficulties in the establishment of the necessary h... Purpose: Peritoneal resection for the therapy of oncological diseases as well as endometriosis is associated with major problems as injury to neighboring organs and difficulties in the establishment of the necessary hemostasis. In this paper we present a new dissection tool, the “Jet Grasper” (KARL STORZ?), which represents a further step towards simple, safe and effective laparoscopic peritoneal resection. Methods: The “Jet Grasper”, was developed to enable selective dissection of the peritoneum and, if necessary, other organs in the case of adhesions. For the tissue resection different techniques can be applied (e.g. ultrasound, mechanical or electrosurgical energy). Results: The tool features a dissection forceps with a narrow slit at the end of the jaw. Further selective dissection is achieved by applying water pressure retroperitoneally via a controlled water pressure pump. Furthermore a diameter difference between the jaw and the sheath potentiates dissection. The thin jaws are introduced precisely to separate and/or dissect layers in a physiological manner to enable further dissection of the peritoneum at a safe distance. Larger vessels can subsequently be targeted for bipolar coagulation in the opened retroperitoneal area. As we are exclusively presenting a completely new device, no patient data are included here. However, a prospective randomized study already started in April 2012, and will be reported after completion in two years. Conlusion: The new dissection tool combines selective dissection and resection under controlled water pressure, known from aquadissection. It provides enhanced and atraumatic possibilities in performing pelvic peritoneal resection via selective dissection and reduction of blood loss. 展开更多
关键词 Jet Grasper Peritoneal Resection COMPLICATION Reduction Aquadissection Laparoscopic Surgery ENDOMETRIOSIS
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