Aim: To test the hypothesis that intraoperative warming (IOW) can improve surgical outcomes after pancreaticoduodenectomy with portal vein reconstruction (PD-PVR). Methods: Patients diagnosed with pancreatic head ductal adenocarcinoma who underwent PD-PVR at Huashan Hospital between January 1, 2017, and January 1, 2022, were retrospectively divided into two groups according to whether IOW was implemented. The primary outcome was the incidence of textbook outcome (TO) after pancreatectomy. The secondary outcomes were intraoperative hypothermia and adjuvant chemotherapy (AC) completion rate. Results: Among the 196 included patients, 122 underwent IOW while 74 did not. Both average (35.2℃ vs. 36.2℃, p < 0.001) and minimum (34.0℃ vs. 35.6℃, p < 0.001) intraoperative body temperature were significantly higher in the IOW group compared with the non-IOW one. Satisfactory surgical outcomes were observed in the IOW group, due to a higher incidence of TOs (51.4% vs. 68.9%, p = 0.021), lower incidence of post-pancreatectomy hemorrhage (13.5% vs. 3.3%, p = 0.010), earlier AC initiation (48 day vs. 40 day, p < 0.001), and AC completion rate (59.5% vs. 76.2%, p = 0.020). IOW was the independent influential factor for TOs, intraoperative hypothermia, and AC completion. In survival analysis, the median overall survival was longer with AC completion (month, 8.6 vs. 27.5, p < 0.001) or TO (month, 16.2 vs. 20.0, p = 0.002). Intraoperative hypothermia (hazard ratio, 1.53; 95% confidence interval: 1.03–2.25, p = 0.033) was the independent risk factor of overall survival. Conclusions: Intraoperative hypothermia occurred frequently in patients with PD-PVR. IOW had a positive impact on surgical outcomes of PD-PVR, resulting in higher rates of TOs and postoperative AC completion.
Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-na & iuml;ve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-na & iuml;ve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (>= 5 mg/l). The most common grade >= 3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.
Surgeries achieving maximal tumor resection remain the major effective treatment of pancreatic cancer. Rapid and precise intraoperative diagnosis of pancreatic tissues is critical for optimum surgical outcomes but is challenging for the current staining-based histological methods. We demonstrated that label-free coherent nonlinear optical microscopy with combined stimulated Raman scattering (SRS) and second harmonic generation (SHG) could reveal key diagnostic features of both normal and cancerous human pancreatic tissues. Adjacent pairs of tissue sections from resection margins of 37 patients were imaged by SRS and hematoxylin and eosin staining for direct comparison, demonstrating high diagnostic concordance (Cohen's kappa, κ > 0.97) between them. Fresh unprocessed tissues showed well-preserved histoarchitectures including pancreatic ducts, islets, acini, and nerves. Moreover, the area ratios of collagen fibers were analyzed and found to correlate with the drainage pancreatic amylase level (odds ratio = 28.0, p = 0.0017). Our results indicated that SRS/SHG histology provides potential for rapid intraoperative diagnosis of pancreatic cancer as well as a predictive value of postoperative pancreatic fistula.
Background: Perioperative glycemic status after pancreatic surgery has never been described. However, it's essential for optimal perioperative glucose management and understanding the pathogenesis of new-onset diabetes mellitus (NODM) after pancreatectomy. Continuous glucose monitoring (CGM) system provides us a helpful tool for closely monitoring and studying perioperative glucose change. This study tried to describe and compare perioperative glucose level and glycemic variability between different types of pancreatic surgeries via CGM device. Methods: This study was designed as a prospective observational study. Eighteen patients were enrolled and were grouped by different types of surgery received: control group (CTRL), pancreaticoduodenectomy (PD), distal pancreatectomy (DP), and total pancreatectomy (TP). CGM devices were implanted and initiated right after the surgery. Mean glucose value (MGV), coefficient of variation (CV), mean of daily difference (MODD), continuous overall net glycemic action (CONGA), and time above range (TAR)/time below range (TBR) was compared between groups to assess glucose level and glycemic variability. Results: TP showed the highest MGV and CV among all groups (P<0.001), while CTRL showed the lowest (P<0.001). PD and DP had similar MGV and CV lower than TP but higher than CTRL (P<0.001). TP had the highest MODD and CONGA, CTRL had the lowest, but no significant differences were found between groups. TP had the highest TAR (24.29%) and the lowest TBR (1.28%), while the control group showed the opposite. The differences in TAR/TBR between groups were all significant (P<0.05). Conclusions: TP had the highest mean glucose level and the greatest glycemic variability. PD and DP had similar results: a higher mean glucose level than control but lower than TP. For glycemic variability, PD and DP seemed to have a near-normal result resembling the control group. CGM is useful for glucose monitoring in the perioperative management of pancreatic surgery.
针对市场客户车门过开失效抱怨偶发,选市场代表车型为样本,设计了车门过开实验方案,对比验证过开性能差异,并总结典型的过开失效模式,重点对限位器干涉玻璃问题进行系统研究,识别出关键影响因子及影响规律,并建立受力分析模型.结果表明:过开角度小于8°,避免限位器臂过长,保证限位器臂与钣金孔间隙不小于5 mm,在空间满足条件下增加翻边结构及Y向匹配等提高安装面刚度,提高车门过开性能.
Background The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages. Methods Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation. Results A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin. Conclusion Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.
Functionalized multi-walled carbon nanotubes have been extensively gained popularity in pancreatic cancer gene therapy. LyP-1, a peptide, has been proved to specifically bind pancreatic cancer cells. The potential therapeutic effect of LyP-1-conjugated functionalized multi-walled carbon nanotubes in treating pancreatic cancer is still unknown. In this study, LyP-1-conjugated functionalized multi-walled carbon nanotubes were successfully synthesized, characterized and showed satisfactory size distribution and zeta potential. Compared with functionalized multi-walled carbon nanotubes, cellular uptake of LyP-1-functionalized multi-walled carbon nanotubes was shown to be increased. Compound of LyP-1-functionalized multi-walled carbon nanotubes and MBD1siRNA showed superior gene transfection efficiency. Moreover, LyP-1-fMWNTs/MBD1siRNA complex could significantly decrease the viability and proliferation and promoted apoptosis of pancreatic cancer cells in vitro. Further xenograft assays revealed that the tumour burden in the nude mice injected with LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA was significantly relieved. The study demonstrated that LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA could be a promising candidate for tumour active targeting therapy in pancreatic cancer.
Rapid histological imaging of pathological tissues with sufficient diagnostic information has great potential to aid doctors in intraoperative decision making. Stimulated Raman scattering (SRS) microscopy is an emerging label -free imaging modality capable of obtaining histological images of tissues without the need for time-consuming tissue processing, such as fixing, sectioning, and staining. An increasing number of studies have demonstrated SRS microscopy as a "virtual histology" tool for rapid diagnosis of various diseases. In this review, we focus on the basic principles and current developments of SRS microscopy as well as its applications for rapid tissue histology.
Background: : Postoperative pancreatic fistula (POPF) is one of the most common complications and the leading cause of morbidity and mortality after pancreatic operation with pancreatojejunostomy (PJ). Many strategies have been used to prevent the incidence of POPF, among which drainage of pancreatic juice is effective. There are two types of drainage methods used in clinical practice; however, the method with a superior effect remains unknown. This study compared the effect of external and internal drainage without stent (in other words, no drainage, only PJ by duct-to-mucosa) on the incidence of clinically relevant POPF (CR-POPF) to provide evidence to select a better drainage scheme in clinical practice. Methods: Overall, 520 patients undergoing pancreatic operation, including PJ were included in this single-centre study and were divided into two groups according to drainage methods. We compared the incidence of CR-POPF between the two groups and performed stratified analysis according to the Fistula Risk Score (FRS) and pancreatic gland texture. Factors such as gender, age, Body Mass Index (BMI), operative procedure, and drainage methods were included in univariable and multivariable analyses. Results: The incidence rate of CR-POPF between two groups was significantly different (23.3% vs 13.6%, P < 0.05). In stratified analysis according to gland texture, a significant difference between the incidence rate of CR-POPF of the two groups was observed in class of 'hard' (5.7% vs 0%, P < 0.05), but in stratified analysis according to FRS, a difference was not observed. There was a statistically significant difference in postoperative hospitalisation (11.00 vs 10.00, P < 0.001) and hospitalisation expense (RMB 86733.28 vs 84085.89 P < 0.05) between the two groups. In multivariable analysis, pancreatoduodenectomy (PD) (odds ratio [OR]= 0.108, 95% confidence interval [CI] 0.038-0.303), pylorus-preserving pancreaticoduodenectomy (OR = 0.070, 95% CI 0.0220.218), and PD with portal vein/superior mesenteric vein reconstruction (OR = 0.137, 95% CI 0.038-0.498) were associated with a decreased incidence of CR-POPF, whereas external drainage (OR = 1.944, 95% CI 1.144-3.305) was associated with an increased incidence of CR-POPF. Conclusions: Compared with internal drainage without stent or only simple PJ by duct-to-mucosa, the external drainage method was associated with a higher incidence of CR-POPF. However, this conclusion needs to be further confirmed in large samples.
基于客户数据制定的整车耐久试验规范,可以使整车产品的考核认证更加合理有效.通过分析电动车在多种操作工况下的性能表现,探讨了电动车动力总成的考核内容;运用抽样统计原理,针对性地分析了与电动车动力总成考核相关的客户数据统计分布,研究了如何将数据分析结果转化为满足客户使用寿命要求的整车耐久试验规范.
Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC. Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported. Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit. Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.
文章首先简要介绍了四立柱台架试验流程,再从轮胎特性和台架响应信号的角度分析了台架位移响应信号的接近特征,通过A、B两车的实际信号分析,证明其台架位移响应信号较为接近.多项目的台架位移信号的统计数据也较为接近.此结论对建立四立柱台架试验标准谱具有重要的指导意义.
BACKGROUND:Total pancreatectomy (TP) is usually considered a therapeutic option for pancreatic cancer in which Whipple surgery and distal pancreatectomy are undesirable, but brittle diabetes and poor quality of life (QoL) remain major concerns. A subset of patients who underwent TP even died due to severe hypoglycemia. For pancreatic cancer involving the pancreatic head and proximal body but without invasion to the pancreatic tail, we performed partial pancreatic tail preserving subtotal pancreatectomy (PPTP-SP) in selected patients, in order to improve postoperative glycemic control and QoL without compromising oncological outcomes.AIM:To evaluate the efficacy of PPTP-SP for patients with pancreatic cancer.METHODS:We retrospectively reviewed 56 patients with pancreatic ductal adenocarcinoma who underwent PPTP-SP (n = 18) or TP (n = 38) at our institution from May 2014 to January 2019. Clinical outcomes were compared between the two groups, with an emphasis on oncological outcomes, postoperative glycemic control, and QoL. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and EORTC PAN26). All patients were followed until May 2019 or until death.RESULTS:A total of 56 consecutive patients were enrolled in this study. Perioperative outcomes, recurrence-free survival, and overall survival were comparable between the two groups. No patients in the PPTP-SP group developed cancer recurrence in the pancreatic tail stump or splenic hilum, or a clinical pancreatic fistula. Patients who underwent PPTP-SP had significantly better glycemic control, based on their higher rate of insulin-independence (P = 0.014), lower hemoglobin A1c (HbA1c) level (P = 0.046), lower daily insulin dosage (P < 0.001), and less frequent hypoglycemic episodes (P < 0.001). Global health was similar in the two groups, but patients who underwent PPTP-SP had better functional status (P = 0.036), milder symptoms (P = 0.013), less severe diet restriction (P = 0.011), and higher confidence regarding future life (P = 0.035).CONCLUSION:For pancreatic cancer involving the pancreatic head and proximal body, PPTP-SP achieves perioperative and oncological outcomes comparable to TP in selected patients while significantly improving long-term glycemic control and QoL.
侧门系统是市场抱怨较多的用户高感知系统之一,本项目是为提高车门系统产品质量和满足精准试验要求而开展的基础研究.文章通过问卷调查和试验模拟,实现了用户开关门行为的调研和记录,完成了开关门状态参数的实时采集.通过积累大量数据并加以分析,得到用户开关门行为的统计学特征,为产品的设计和验证提供参考和支持,进而为产品质量提升提供助力.
针对汽车多通道台架耐久试验中轮心六分力测量参数需求,设计了一种基于多传感器并联结构的车轮六轴力测量轮,同时开发了信号调理模块以及相应的自动化标定系统.标定试验结果表明:该测量系统的测力精度为0.5级,最大串扰为0.67%FS.最后,在MTS329台架上,本测量系统与进口MSC测量轮进行了对标,结果表明:各轴最大相对误差为2.51%FS,最大非线性误差为2.29%FS,满足台架试验需求.
Objective: Brain is a fantastic organ that helps creature adapting to the environment. Network is the most essential structure of brain, but the capability of a simple network is still not very clear. In this study, we try to expound some brain functions only by the network property. Methods: Every network can be equivalent to a simplified network, which is expressed by an equation set. The dynamic of the equation set can be described by some basic equations, which is based on the mathematical derivation. Results (1) In a closed network, the stability is based on the excitatory/inhibitory synapse proportion. Spike probabilities in the assembly can meet the solution of a nonlinear equation set. (2) Network activity can spontaneously evolve into a certain distribution under different stimulation, which is closely related to decision making. (3) Short memory can be formed by coupling of network assemblies. Conclusion: The essential property of a network may contribute to some important brain functions.
通过对车辆大数据的分析,针对某混动车型发动机散热器的温度冲击失效模式,研究了温度冲击的影响因素并设计了专项试验,建立了散热器的温度冲击模型.通过该模型,分析并统计了客户工况下的温度冲击数据.按正态分布验证并计算温度冲击循环次数理论值,并以此为基础开发了覆盖此种用户工况的整车考核规范.
载荷谱是当前道路模拟试验研究的重点.针对传统实车路谱数据采集及全虚拟仿真的局限性,文章提出了基于数字路面、轮胎模型、台架、试验车等的混合试验方法,研究了混合试验系统建模及迭代方法,并据此开展实车试验,最后对混合试验与实车道路试验轮心载荷进行了相关性分析.结果表明,该方法与实车道路试验具有较好的一致性,可大幅提前整车结构耐久性评估的节点,为压缩项目开发周期提供了有效手段.
乘用车在生命周期中会受到多种环境因素影响,其中,温度、湿度、振动这3种因素的影响最大.为了尽量精准地模拟产品生命周期中可能经历的环境工况,相关研究人员设计了一种"温度—湿度—振动—光照"综合环境模拟试验.文章详细描述了试验系统的构成以及温度、湿度、光照和振动等试验参数的设计过程.通过实车试验验证可知,该试验系统可靠,各参数设计准确,可以为后续产品设计提供理论基础,加强品质提升和成本管理.
Maximal resection of tumor while preserving the adjacent healthy tissue is particularly important for larynx surgery, hence precise and rapid intraoperative histology of laryngeal tissue is crucial for providing optimal surgical outcomes. We hypothesized that deep-learning based stimulated Raman scattering (SRS) microscopy could provide automated and accurate diagnosis of laryngeal squamous cell carcinoma on fresh, unprocessed surgical specimens without fixation, sectioning or staining. Methods: We first compared 80 pairs of adjacent frozen sections imaged with SRS and standard hematoxylin and eosin histology to evaluate their concordance. We then applied SRS imaging on fresh surgical tissues from 45 patients to reveal key diagnostic features, based on which we have constructed a deep learning based model to generate automated histologic results. 18,750 SRS fields of views were used to train and cross-validate our 34-layered residual convolutional neural network, which was used to classify 33 untrained fresh larynx surgical samples into normal and neoplasia. Furthermore, we simulated intraoperative evaluation of resection margins on totally removed larynxes. Results: We demonstrated near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) between SRS and standard histology as evaluated by three pathologists. And deep-learning based SRS correctly classified 33 independent surgical specimens with 100% accuracy. We also demonstrated that our method could identify tissue neoplasia at the simulated resection margins that appear grossly normal with naked eyes. Conclusion: Our results indicated that SRS histology integrated with deep learning algorithm provides potential for delivering rapid intraoperative diagnosis that could aid the surgical management of laryngeal cancer.