Identifying the risk factors for pancreatic fistula after laparoscopic pancreaticoduodenectomy in patients with pancreatic cancer

BACKGROUND Laparoscopic pancreaticoduodenectomy(LPD)is a surgical procedure for treating pancreatic cancer;however,the risk of complications remains high owing to the wide range of organs involved during the surgery and the difficulty of anastomosis.Pancreatic fistula(PF)is a major complication that not only increases the risk of postoperative infection and abdominal hemorrhage but may also cause multi-organ failure,which is a serious threat to the patient’s life.This study hypothesized the risk factors for PF after LPD.AIM To identify the risk factors for PF after laparoscopic pancreatoduodenectomy in patients with pancreatic cancer.METHODS We retrospectively analyzed the data of 201 patients admitted to the Fudan University Shanghai Cancer Center between August 2022 and August 2023 who underwent LPD for pancreatic cancer.On the basis of the PF’s incidence(grades B and C),patients were categorized into the PF(n=15)and non-PF groups(n=186).Differences in general data,preoperative laboratory indicators,and surgery-related factors between the two groups were compared and analyzed using multifactorial logistic regression and receiver-operating characteristic(ROC)curve analyses.RESULTS The proportions of males,combined hypertension,soft pancreatic texture,and pancreatic duct diameter≤3 mm;surgery time;body mass index(BMI);and amylase(Am)level in the drainage fluid on the first postoperative day(Am>1069 U/L)were greater in the PF group than in the non-PF group(P<0.05),whereas the preoperative monocyte count in the PF group was lower than that in the non-PF group(all P<0.05).The logistic regression analysis revealed that BMI>24.91 kg/m²[odds ratio(OR)=13.978,95%confidence interval(CI):1.886-103.581],hypertension(OR=8.484,95%CI:1.22-58.994),soft pancreatic texture(OR=42.015,95%CI:5.698-309.782),and operation time>414 min(OR=15.41,95%CI:1.63-145.674)were risk factors for the development of PF after LPD for pancreatic cancer(all P<0.05).The areas under the ROC curve for BMI,hypertension,soft pancreatic texture,and time prediction of PF surgery were 0.655,0.661,0.873,and 0.758,respectively.CONCLUSION BMI(>24.91 kg/m²),hypertension,soft pancreatic texture,and operation time(>414 min)are considered to be the risk factors for postoperative PF.

Anatomical features and technical difficulties in laparoscopic pancreaticoduodenectomy with various superior mesenteric artery-first approaches

Laparoscopic pancreaticoduodenectomy(LPD) at its early stage failed to demonstrate the superiority compared with open pancreaticoduodenectomy(OPD) [1]. The well-known randomized trial, LEOPARD-2, was even terminated due to the safety issue [2], but recent researches [3,4] revealed that LPD is technically safe and feasible with acceptable rates of morbidity and mortality and therefore, gains popularity recently.

高层建筑基础底板大体积混凝土冬季施工技术研究与应用

针对大体积混凝土冬季施工的特点,通过分析研究材料和温度对大体积混凝土冬季施工的影响,设计和优化冬季施工方案,并结合实际工程案例研究北方民用建筑大体积混凝土冬季施工技术。结果表明,通过施工方案的优化和精心的施工组织管理,可以避免大体积混凝土冬季施工过程中裂缝的产生,确保地下结构冬季的施工质量。

城市公园用户的情绪特征及影响因子研究——以华南植物园和越秀公园为例

以广州市华南植物园和越秀公园为例,分析公园用户的情绪特征,并基于结构方程模型,探究城市公园用户情绪的影响因子及驱动机制。研究结果表明,公园用户的积极情绪相对较高,但积极情绪和消极情绪是独立存在的。对于粗粒度情绪,景观要素有直接影响和间接影响两种方式;对于细粒度情绪,景观要素主要通过景观服务,间接地影响用户情绪感知。不同类型公园中,用户的不同类型、不同粒度情绪的影响因素及机制均存在差异。研究结果可以对公园的规划设计提出具有针对性的改进方案,并为城市其他类型空间使用者的情绪研究提供一定的借鉴。

Acetyl-11-keto-β-boswellic acid inhibits proliferation and induces apoptosis of gastric cancer cells through the phosphatase and tensin homolog/Akt/cyclooxygenase-2 signaling pathway

BACKGROUND Gastric cancer is one of the most common malignant tumors of the digestive system worldwide,posing a serious danger to human health.Cyclooxygenase(COX)-2 plays an important role in the carcinogenesis and progression of gastric cancer.Acetyl-11-keto-β-boswellic acid(AKBA)is a promising drug for cancer therapy,but its effects and mechanism of action on human gastric cancer remain unclear.AIM To evaluate whether the phosphatase and tensin homolog(PTEN)/Akt/COX-2 signaling pathway is involved in the anti-tumor effect of AKBA in gastric cancer.METHODS Human poorly differentiated BGC823 and moderately differentiated SGC7901 gastric cancer cells were routinely cultured in Roswell Park Memorial Institute 1640 medium supplemented with 10%fetal bovine serum and 1%penicillin/streptomycin.Gastric cancer cell proliferation was determined by methyl thiazolyl tetrazolium colorimetric assay.Apoptosis was measured by flow cytometry.Cell migration was assessed using the wound-healing assay.Expression of Bcl-2,Bax,proliferating cell nuclear antigen,PTEN,p-Akt,and COX-2 were detected by Western blot analysis.A xenograft nude mouse model of human gastric cancer was established to evaluate the anti-cancer effect of AKBA RESULTS AKBA significantly inhibited the proliferation of gastric cancer cells in a dose-and time-dependent manner,inhibited migration in a time-dependent manner,and induced apoptosis in a dose-dependent manner in vitro;it also inhibited tumor growth in vivo.AKBA up-regulated the expression of PTEN and Bax,and downregulated the expression of proliferating cell nuclear antigen,Bcl-2,p-Akt,and COX-2 in a dose-dependent manner.The PTEN inhibitor bpv(Hopic)reversed the high expression of PTEN and low expression of p-Akt and COX-2 that were induced by AKBA.The Akt inhibitor MK2206 combined with AKBA downregulated the expression of p-Akt and COX-2,and the combined effect was better than that of AKBA alone.CONCLUSION AKBA inhibits the proliferation and migration and promotes the apoptosis of gastric cancer cells through the PTEN/Akt/COX-2 signaling pathway.

Optimization by orthogonal array design of ion-pair HPLC separation of the enzymatic hydrolysis products of yeast RNA

The separation of enzymatic hydrolysis products of yeast RNA by ion-pair HPLC was studied.A modified chromatographic response function（MCRF） was proposed to appraise the effectiveness of chromatographic separation.This function takes the number of peaks,resolution and the retention time of the last peak into consideration.It shows advantages for optimization of HPLC separation of complex mixtures.An orthogonal array design was used to separate the hydrolysate of yeast RNA and the optimal chromatographic conditions were obtained.

Development and multicenter validation of a nomogram for preoperative prediction of lymph node positivity in pancreatic cancer(NeoPangram)

Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease.Methods:A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts.Multivariate logistic regression analysis was used to construct the nomogram.Model performance was evaluated by discrimination,calibration,and clinical usefulness.An independent multicenter cohort consisting of 250 patients was used for external validation.Results:A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9),CA125,CA50,and CA242.A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis:risk score of the four-marker signature,computed tomography-reported LN status,and clinical tumor stage.The prediction model exhibited good discrimination ability,with C-indexes of 0.806,0.742 and 0.763 for the development,internal validation,and external validation cohorts,respectively.The model also showed good calibration and clinical usefulness.A cut-off value(0.72)for the probability of LN metastasis was determined to separate low-risk and high-risk patients.Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status.Conclusions:This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.

Validation and head-to-head comparison of four models for predicting malignancy of intraductal papillary mucinous neoplasm of the pancreas: A study based on endoscopic ultrasound findings

BACKGROUND Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm(IPMN),namely,the Pancreatic Surgery Consortium(PSC),the Japan Pancreas Society(JPS),the Johns Hopkins Hospital(JHH),and the Japan-Korea(JPN-KOR)models.However,a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking.AIM To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN.METHODS A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database.The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives.The performance of all four models was examined using Harrell’s concordance index(C-index),calibration plots,decision curve analyses,and diagnostic tests.RESULTS Of the 181 included patients,94 were categorized as having benign disease,and the remaining 87 were categorized as having malignant disease.The C-indexes were 0.842[95%confidence interval(CI):0.782-0.901],0.704(95%CI:0.626-0.782),0.754(95%CI:0.684-0.824),and 0.650(95%CI:0.483-0.817)for the PSC,JPS,JHH,and JPN-KOR models,respectively.Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions.Of the remaining three models,the JPS and JHH models underestimated the probability of malignancy,while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN.Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models.Diagnostic tests also showed a higher accuracy(0.801)for the PSC model.CONCLUSION The PSC model exhibited the best performance characteristics.Therefore,the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.

Application of endoscopic ultrasonography for detecting esophageal lesions based on convolutional neural network

BACKGROUND A convolutional neural network(CNN) is a deep learning algorithm based on the principle of human brain visual cortex processing and image recognition.AIM To automatically identify the invasion depth and origin of esophageal lesions based on a CNN.METHODS A total of 1670 white-light images were used to train and validate the CNN system.The method proposed in this paper included the following two parts:(1)Location module,an object detection network,locating the classified main image feature regions of the image for subsequent classification tasks;and(2) Classification module,a traditional classification CNN,classifying the images cut out by the object detection network.RESULTS The CNN system proposed in this study achieved an overall accuracy of 82.49%,sensitivity of 80.23%,and specificity of 90.56%.In this study,after follow-up pathology,726 patients were compared for endoscopic pathology.The misdiagnosis rate of endoscopic diagnosis in the lesion invasion range was approximately 9.5%;41 patients showed no lesion invasion to the muscularis propria,but 36 of them pathologically showed invasion to the superficial muscularis propria.The patients with invasion of the tunica adventitia were all treated by surgery with an accuracy rate of 100%.For the examination of submucosal lesions,the accuracy of endoscopic ultrasonography(EUS) was approximately 99.3%.Results of this study showed that EUS had a high accuracy rate for the origin of submucosal lesions,whereas the misdiagnosis rate was slightly high in the evaluation of the invasion scope of lesions.Misdiagnosis could be due to different operating and diagnostic levels of endoscopists,unclear ultrasound probes,and unclear lesions.CONCLUSION This study is the first to recognize esophageal EUS images through deep learning,which can automatically identify the invasion depth and lesion origin of submucosal tumors and classify such tumors,thereby achieving good accuracy.In future studies,this method can provide guidance and help to clinical endoscopists.

A visual modeling method for spatiotemporal and multidimensional features in epidemiological analysis:Applied COVID-19 aggregated datasets

The visual modeling method enables flexible interactions with rich graphical depictions of data and supports the exploration of the complexities of epidemiological analysis.However,most epidemiology visualizations do not support the combined analysis of objective factors that might influence the transmission situation,resulting in a lack of quantitative and qualitative evidence.To address this issue,we developed a portrait-based visual modeling method called+msRNAer.This method considers the spatiotemporal features of virus transmission patterns and multidimensional features of objective risk factors in communities,enabling portrait-based exploration and comparison in epidemiological analysis.We applied+msRNAer to aggregate COVID-19-related datasets in New South Wales,Australia,combining COVID-19 case number trends,geo-information,intervention events,and expert-supervised risk factors extracted from local government area-based censuses.We perfected the+msRNAer workflow with collaborative views and evaluated its feasibility,effectiveness,and usefulness through one user study and three subject-driven case studies.Positive feedback from experts indicates that+msRNAer provides a general understanding for analyzing comprehension that not only compares relationships between cases in time-varying and risk factors through portraits but also supports navigation in fundamental geographical,timeline,and other factor comparisons.By adopting interactions,experts discovered functional and practical implications for potential patterns of long-standing community factors regarding the vulnerability faced by the pandemic.Experts confirmed that+msRNAer is expected to deliver visual modeling benefits with spatiotemporal and multidimensional features in other epidemiological analysis scenarios.

Signaling pathways in cancer-associated fibroblasts:recent advances and future perspectives

As a critical component of the tumor microenvironment(TME),cancerassociated fibroblasts(CAFs)play important roles in cancer initiation and progression.Well-known signaling pathways,including the transforming growth factor-β(TGF-β),Hedgehog(Hh),Notch,Wnt,Hippo,nuclear factor kappa-B(NF-κB),Janus kinase(JAK)/signal transducer and activator of transcription(STAT),mitogen-activated protein kinase(MAPK),and phosphoinositide 3-kinase(PI3K)/AKT pathways,as well as transcription factors,including hypoxia-inducible factor(HIF),heat shock transcription factor 1(HSF1),P53,Snail,and Twist,constitute complex regulatory networks in theTMEtomodulate the formation,activation,heterogeneity,metabolic characteristics and malignant phenotype of CAFs.Activated CAFs remodel the TME and influence the malignant biological processes of cancer cells by altering the transcriptional and secretory characteristics,and this modulation partially depends on the regulation of signaling cascades.The results of preclinical and clinical trials indicated that therapies targeting signaling pathways in CAFs demonstrated promising efficacy but were also accompanied by some failures(e.g.,NCT01130142 and NCT01064622).Hence,a comprehensive understanding of the signaling cascades in CAFs might help us better understand the roles of CAFs and the TME in cancer progression and may facilitate the development of more efficient and safer stroma-targeted cancer therapies.Here,we review recent advances in studies of signaling pathways in CAFs and briefly discuss some future perspectives on CAF research.

Photoactivated CRY1 and phyB Interact Directly with AUX/IAA Proteins to Inhibit Auxin Signaling in Arabidopsis

Light is a key environmental cue that inhibits hypocotyl cell elongation through the blue and red/far-red light photoreceptors cryptochrome- and phytochrome-mediated pathways in Arabidopsis. In contrast, as a pivotal endogenous phytohormone auxin promotes hypocotyl elongation through the auxin receptors TIR1/AFBs-mediated degradation of AUX/IAA proteins （AUX/IAAs）. However, the molecular mechanisms underlying the antagonistic interaction of light and auxin signaling remain unclear. Here, we report that light inhibits auxin signaling through stabilization of AUX/IAAs byblue and red light-dependent interactions of cryptochrome 1 （CRY1） and phytochrome B with AUX/IAAs, respectively. Blue light-triggered interactions of CRY1 with AUX/IAAs inhibit the associations of TIR1 with AUX/IAAs, leading to the repression of auxin- induced degradation of these proteins. Our results indicate that photoreceptors share AUX/IAAs with auxin receptors as the same direct downstream signaling components. We propose that antagonistic regulation of AUX/IAA protein stability by photoreceptors and auxin receptors allows plants to balance light and auxin signals to optimize their growth.

Chemical constituents and pharmacological effects of genus Engelhardia

Engelhardia Leschen. ex Blume （Juglandaceae） is native to southern and southeastern Asia and used to be traditional medicines and health tea. Hitherto, a large amount of chemical constituents had been iso- lated from genus Engelhardia and more pharmacological effects were found due to the presence of the second metabolites. There have been few comprehensive reports about Engelhardia plants especially the chemical constituents by now. The traditional usage of Engelhardia plants were for treating cold fever, detoxication, rheumatism, diarrhea, obesity, gastrointestinal problem and so on. While the modern pharmacological activities showed antioxidant activity, anti-ischemialreperfusion injury, anticancer activity, anti-inflammatory activity, immunosuppression activity, antidiabetic activity, antitubercular activity and so on. In this review, constituents of this genus would be introduced and classified by structures, the pharmacological effects of which would be described as well.

Silica nanoparticle with a single His-tag for addressable functionalization, reversible assembly, and recycling

For many biomedical and catalytic applications, such as encapsulation of proteins/enzymes in nanopartides （NPs）, it is preferable to have well-dispersed small NPs that are stable in solution and behave quasi-homogeneously. However, conventional liquid phase methods for small-NP synthesis and functionalization usually face great difficulties in separation/purification and recycling. In addition, controlling the orientation of proteins inside NPs is also a crucial issue to maximize the activity of the encapsulated proteins. Herein, we report a solid phase method to solve these problems. Using His-tagged proteins as cores, well-dispersed core-sheU silica NPs are facilely synthesized and functionalized in a column. The core His-tagged proteins are kept bound on the surface of the resIn beads in the column during the entire process, making the separation/purification of NPs and their precursors during the multiple-step process as simple as a few-minutes procedure of draining and washing the column. Each obtained silica NP has an adjustable eccentric core-shell structure with only one His-tag sticking out of the particle. This single His-tag on the surface of each NP not only makes it easy for addressable and stoichiometric functionalization of the NP but also provides an easy way to reversibly assemble NPs into dimers or be oriented on the surface of large particles. Notably, this solid phase approach also provides a versatile means to control the orientation of proteins inside NPs, and the His-tag makes it easy to recycle those well-dispersed small NPs.

Discovery of lung squamous carcinoma biomarkers by profiling the plasma peptide with LC/MS/MS

Biomarkers can be used for the screening and clinical diagnosis of cancer,and peptidomics approach has been proven successful in the research of biomarkers.To develop better peptidomic technologies for fast,accurate,and reliable detection of peptides biomarkers for lung cancer,we have improved the procedures of blood collection to minimize the degradation of the blood proteins and optimize the extraction of peptidome peptides from plasma samples based on acetonitrile precipitation associated with size exclusion chromatography（SEC）.Studies show that squamous cell carcinomas are found to express CAGEl,SPAT9 and TEX28 genes at significantly higher rates,and the results suggest that as tumors progress,the level of CAGEl,SPAT9 and TEX28 genes are likely to increase and lead to immunization.This suggests a potentially important therapeutic method for cancer testis-based cancer vaccines.