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Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.

Purpose: To investigate whether multiparametric quantitative diffusion weighted magnetic resonance imaging (DWI) can effectively predict the neoadjuvant therapy (NAT) response in borderline resectable pancreatic ductal adenocarcinoma (BRPC)., Methods: The clinicopathological data, including tumor size, location, and CA19-9 values, as well as DWI parameters(ADC, D, and f values) from 72 patients with BRPC, were analyzed. The differences and changes in these factors before and after NAT were compared to identify those most accurately reflect the response to NAT. ROC analysis was used to evaluate the diagnostic efficacy, and Kaplan-Meier survival analysis explored the relationship between DWI parameters and prognosis. Subgroup survival analysis to further identify populations potentially benefiting from NAT based on multiparametric DWI., Results: After-NAT, the response group showed significantly higher ADC and D values and lower f values compared to the non-response group. The ΔADC (OR: 12.24, P = 0.013) emerged as the most important independent factor for tumor response, demonstrating the highest diagnostic accuracy for NAT response with an AUC of 0.936. Kaplan-Meier showed the high ADC value group, high D value group and low f value group were associated with better prognosis after NAT; and the ΔADC ≥ 0 group, ΔD ≥ 0 group, and Δf < 0 group was significantly associated with better prognosis. In addition, subgroup analysis suggested two groups of patients might potentially benefit from NAT., Conclusions: Multiparametric quantitative DWI may offer valuable insights into the efficacy and prognosis of NAT in BRPC. These findings have the potential to support the evaluation and decision-making process for patients undergoing NAT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) frequently metastasizes to the liver, significantly worsening patient outcomes. While hepatectomy offers the best curative option for colorectal liver metastases (CRLM), margin recurrence remains a major challenge post-surgery. Intraoperative ultrasound (IOUS) aids tumor identification and margin determination, but its limitations in laparoscopic surgery necessitate additional methods. Indocyanine green fluorescence imaging (ICGFI) has emerged as a promising tool for tumor localization and margin assessment in CRLM. However, existing studies lack large cohorts and long-term outcomes. This study evaluates perioperative and long-term results of ICGFI-assisted laparoscopic hepatectomy in CRLM patients., Method: A retrospective cohort study was performed on CRLM patients who underwent liver resection at our single center. The study population was divided into three groups: the L-ICG group (laparoscopic hepatectomy with ICGFI), the L-Non-ICG group (laparoscopic hepatectomy without ICGFI), and the open group (open liver resection). Robust statistical methods including multiple imputations and inverse probability of treatment weighting (IPTW) were employed to minimize bias., Results: A total of 340 CRLM patients who underwent hepatectomy were analyzed. The L-ICG group had a higher rate of neoadjuvant therapy and smaller tumor sizes compared to the open group. The L-ICG group also demonstrated shorter operative times, less blood loss, and a higher microscopically margin-negative (R0) resection rate than other two groups. Recurrence occurred in 70% of patients, with 77% being intrahepatic. Margin recurrence was significantly lower in the L-ICG group compared to the L-Non-ICG group (15.3% vs. 45.7%, p = 0.001). Median recurrence-free survival and overall survival did not differ significantly among groups after IPTW adjustment., Conclusion: ICGFI improves R0 resection rates, perioperative outcomes, and reduces margin recurrence in CRLM patients undergoing laparoscopic hepatectomy, though it does not significantly impact OS or RFS., Competing Interests: Declarations. Disclosures: Gaoming Wang, Chenghao Liu, Weijun Qi, Long Li, and Dianrong Xiu have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP., Methods: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed., Results: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion., Conclusion: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage., (Copyright © 2024. Published by Elsevier Ltd.)

The distribution and diversity of woody vegetation are crucial for understanding the structure and ecology of urban forests. As urbanization accelerates, the construction and composition of urban forests vary significantly along the urban-rural gradient. Qingdao's urban forests offer an opportunity to test the relationship between the diversity of woody plants and the urban-rural gradient. We classified the urban-rural gradient using imperviousness and construction time, then investigated the diversity of woody plants in Qingdao's urban forests under different urban-rural gradients and tested the reasonableness of their allocation. Correlation analysis found that the diversity index of woody plants in urban forests was highly connected to the urban-rural gradient (by imperviousness: r Margalef Index  = -0.589, r Shannon-Wiener Index  = -0.373, r Pielou Index  = -0.170, r Simpson Index  = 0.272/by construction time: r Margalef Index  = -0.530, r Shannon-Wiener Index  = -0.360, r Pielou Index  = -0.148, r Simpson Index  = 0.272/0.174). With a decrease in urbanization density, the Margalef ( H ), Shannon-Wiener ( H' ), and Simpson ( D ) indices all decreased while the Pielou ( E ) index increased. The four diversity indices showed a substantial correlation with one another, but not with the Margalef and Pielou indices. The analysis utilizing the 10/20/30 rule of empirical demonstrates a clear irrationality in allocating shrub species in Qingdao's urban forests, and the distribution of tree species is reasonable. Based on the study results, strategies for optimizing and enhancing urban forests in Qingdao are proposed for different urban-rural gradients, respectively. This study can provide a scientific framework for urban biodiversity conservation and management in Qingdao and serve as a guide for urban forests and greening with comparable climates., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Lianyuan Tao,1,2 Li Su,3 Chunhui Yuan,1 Zhaolai Ma,1 Lingfu Zhang,1 Shiping Bo,4 Yunyun Niu,4 Sijia Lu,4 Dianrong Xiu11Department of General Surgery, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 4Department of Clinical Research, Yikon Genomics Co. Ltd., Shanghai, People’s Republic of ChinaPurpose: The aim of this study was to evaluate the value of flow cytometry (FCM) detection of portal vein circulating tumor cells (CTCs) in predicting postoperative metastasis.Methods: Samples of portal venous blood and peripheral blood were collected from 39 patients during surgery, and CTCs were detected by FCM, with confirmation by laser confocal microscopy and single-cell sequencing.Results: Among all patients, a portal EpCAM+CD45- percentage ≥24.5×10−4 (P=0.06), peripheral EpCAM+CD45- count ≥97/5 mL (P=0.034), peripheral EpCAM+CD45- percentage ≥4.4×10−4 (P=0.042), and CA242≥3.5 U/mL (P=0.027) were significant predictors of metastasis. Further analysis showed that the portal EpCAM+CD45- ratio ≥24.5×10−4 is a predictor of metastasis (P=0.025) in pancreatic cancer after curative resection.Conclusion: CTCs detected by FCM in portal venous blood are of significant value for the prediction of postoperative metastasis in pancreatic or periampullary tumors.Keywords: circulating tumor cells, flow cytometry, portal vein, pancreatic cancer, metastases

Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two-back WM task (n = 443, 189M/254F) and T1 MRI data (n = 320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = -0.118, t = -2.367, P = 0.019, and the left hippocampus: β = -0.099, t = -1.949, P = 0.052) and better WM performance (β = -0.110, t = -2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population-specific genetic effects.

Lingfu Zhang,1 Lianyuan Tao,1 Limei Guo,2 Jun Zhan,3 Chunhui Yuan,1 Zhaolai Ma,1 Bin Jiang,1 Dianrong Xiu1 1Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, People’s Republic of China Background: Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC.Materials and methods: The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P

Listening to natural sounds, both live and recorded, in either a natural or built environment is considered natural sound exposure (NSE). Sound is closely related to daily life, and research on the restorative effects of natural sounds is expanding. However, there is a lack of quantitative and comprehensive analysis on the impact of NSE on health recovery. This study systematically reviewed and conducted a meta-analysis on the impact of NSE on health recovery. Fifteen studies (1285 participants) were selected for the meta-analysis out of the 1157 literatures about the recovery of the NSE, searched from the Web of Science and Science Direct. The results indicate that NSE has certain positive effects: (a) In terms of emotional changes, NSE significantly reduces anxiety as measured by both the Visual Analog Scale (VAS) -2.31 (95 % CI -2.83, -1.79) and the State Anxiety Inventory (SAI) -12.22 (95 % CI -22.46, -1.98). (b) In terms of physiological reaction, NSE resulted in reduced heart rate (HR) -5.46 (95 % CI -9.62, -1.31), systolic blood pressure (SBP) -11.74 (95 % CI -15.51, -7.97), diastolic blood pressure (DBP) -13.98 (95 % CI -24.96, -2.99) and respiratory rate (RR) -1.58 (95 % CI -3.06, -0.10). (c) While the potential for restoration of cognitive performance by NSE was found, no consistent conclusions have been reached yet. However, there was significant heterogeneity between studies, primarily attributed to variations in study populations and methodologies. Because of the limited literature, we did not conduct subgroup analysis and meta-regression analysis. It is recommended that future studies address this heterogeneity by including more and higher-quality literature and employing rigorous methodologies to establish a robust foundation for evidence-based medicine. This will be of great significance for the application natural sounds in landscape planning and medical rehabilitation environments, and has the potential to promote improvements in public health., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigated the association between prolonged grief (PG) severity and meaning-making narration in a cross-cultural context, and specifically aimed to illustrate the role of value orientation in shaping the grieving process. 30 Chinese and 22 Swiss parents who lost their child were asked to narrate and appraise specific memories to reflect their self-evaluation of traditional and modern values. The self-reported Prolonged Grief Disorder Scale (ref ICD-11) assessed PG severity. Compared with the Swiss sample, the Chinese sample provided more elaborated memories, which was not associated with symptom severity. Both Chinese and Swiss bereaved parents with more severe PG provided more narratives of loss-related memories, particularly in response to modern values. They also provided more appraisals of negative meanings for self-defining memories, particularly in relation to their traditional values. These findings indicate that, despite cultural differences in narration tendency, PG severity in bereaved parents was associated with the maladaptive integration of autobiographical memories across different cultures, in relation to value orientations. A clinical implication is the potential value of facilitating narrations of grieving clients that center on value orientations to mitigate the hardship of the personal loss., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Robotic distal pancreatectomy (RDP) is associated with a lower conversion rate and less blood loss than laparoscopic distal pancreatectomy (LDP). LDP has similar oncological outcomes as open surgery in PDAC. The aim of this study was to compare perioperative and oncological outcomes in obese patients with RDP versus LDP for PDAC., Materials and Methods: Retrospectively, all obese patients who underwent RDP or LDP for PDAC between 2012 and 2022 at 12 international expert centres were included., Results: out of 372, 81 patients were included. All baseline features were comparable between the two groups. RDP was associated with decreased blood loss (495mlLDP vs. 188mlRDP; p = 0.003), lower conversion rate (13.5%RDP vs. 36.4%LDP; p = 0.019) and lower rate of Clavien-Dindo ≥3 complications (13.5%RDP vs. 36.4%LDP; p = 0.019). Overall and disease-free survival were comparable., Conclusions: In obese patients with left-sided PDAC, the robotic approach was associated with improved intraoperative outcomes and fewer severe complications., (© 2023 John Wiley & Sons Ltd.)

Background: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30., Methods: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias., Results: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD., Conclusions: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD., (© 2023. The Author(s).)

Objective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis., Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models., Results: Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs . 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs . 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins., Conclusions: These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Multicolor two-photon endomicroscopy has become a highly competitive tool for functional imaging in biomedical researches. However, to make the imaging system miniature and applicable for freely behaving animal brain activity, metalenses have received much attention in compact imaging systems. For high resolution multicolor imaging and maximizing fluorescence collection, there is a challenge metalenses faced to achieve large numerical aperture (NA) and focus the NIR excitation and VIS emission lights of multiple fluorophores to the same distance simultaneously because of the limitation of the group delay range of the meta-units. In this paper, we proposed a high NA and polarization-insensitive ultra-broadband achromatic metalens specifically for achromatically focusing the excitation and emission light of multiple fluorophores commonly used in neuroscience studies. TiO 2 and Si meta-unit libraries composed of heights, widths and the corresponding phase and group delay were constructed, and the optimal meta-units were selected by particle swarm optimization algorithm to engineer the dispersion of metalens in the VIS band and NIR band, respectively. Combining dispersion engineering with spatial multiplexing, the proposed metalens achieved the maximal effective NA up to 0.8 and large achromatic bandwidth ranging from 500 nm to 1050 nm, which exhibited the coefficient of variation of focal lengths was only 3.41%. The proposed achromatic metalens could successfully achromatically focus different fluorescence with any polarization, which was suitable for most fluorophores. Our results firmly establish that the proposed metalens can open the door to high resolution and minimally invasive multicolor two-photon functional imaging in intravital deep brain.

Introduction: Postoperative pancreatic fistula (POPF) remains one of the main complications following pancreatic resection. Despite pancreatic fistula having a low postoperative mortality rate, the readmission and intervention rates in patients with pancreatic fistula are still considerable. Although there are several studies on pancreatic fistula development after pancreaticoduodenectomy, there are only a few studies on the feeding protocols applied after distal pancreatectomy or enucleation of pancreatic tumours. We designed this trial to test the hypothesis that early feeding does not increase the incidence of POPF and positively influences the long-term prognosis in patients who undergo distal pancreatectomy or enucleation of pancreatic tumours., Methods and Analysis: This is a prospective randomised controlled trial that will be conducted in a single centre. A total of 106 patients undergoing distal pancreatectomy or enucleation of pancreatic tumours will be recruited after providing informed consent. They will be randomly assigned to either an early or late feeding group. The early feeding group will begin enteral nutrition on postoperative day (POD) 3, and the late feeding group will begin enteral nutrition on POD7. The primary outcome is the incidence of POPF. The secondary outcomes include the length of postoperative hospital stay, postoperative complications, and indicators of long-term prognosis., Ethics and Dissemination: Peking University Third Hospital Medical Science Research Ethics Committee approved the study (M2021395). Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice., Trial Registration Number: ChiCTR2100053978., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The preoperative prediction of lymph node metastasis (LNM) in pancreatic ductal adenocarcinoma (PDAC) is essential in prognosis and treatment strategy formulation., Purpose: To compare the performance of computed tomography (CT) and magnetic resonance imaging (MRI) radiomics models for the preoperative prediction of LNM in PDAC., Material and Methods: In total, 160 consecutive patients with PDAC were retrospectively included, who were divided into the training and validation sets (ratio of 8:2). Two radiologists evaluated LNM basing on morphological abnormalities. Radiomics features were extracted from T2-weighted imaging, T1-weighted imaging, and multiphase contrast enhanced MRI and multiphase CT, respectively. Overall, 1184 radiomics features were extracted from each volume of interest drawn. Only features with an intraclass correlation coefficient ≥0.75 were included. Three sequential feature selection steps-variance threshold, variance thresholding and least absolute shrinkage selection operator-were repeated 20 times with fivefold cross-validation in the training set. Two radiomics models based on multiphase CT and multiparametric MRI were built with the five most frequent features. Model performance was evaluated using the area under the curve (AUC) values., Results: Multiparametric MRI radiomics model achieved improved AUCs (0.791 and 0.786 in the training and validation sets, respectively) than that of the CT radiomics model (0.672 and 0.655 in the training and validation sets, respectively) and of the radiologists' assessment (0.600-0.613 and 0.560-0.587 in the training and validation sets, respectively)., Conclusion: Multiparametric MRI radiomics model may serve as a potential tool for preoperatively evaluating LNM in PDAC and had superior predictive performance to multiphase CT-based model and radiologists' assessment.

Mathematical equations are often used to model biological processes. However, for many systems, determining analytically the underlying equations is highly challenging due to the complexity and unknown factors involved in the biological processes. In this work, we present a numerical procedure to discover dynamical physical laws behind biological data. The method utilizes deep learning methods based on neural networks, particularly residual networks. It is also based on recently developed mathematical tools of flow-map learning for dynamical systems. We demonstrate that with the proposed method, one can accurately construct numerical biological models for unknown governing equations behind measurement data. Moreover, the deep learning model can also incorporate unknown parameters in the biological process. A successfully trained deep neural network model can then be used as a predictive tool to produce system predictions of different settings and allows one to conduct detailed analysis of the underlying biological process. In this paper, we use three biological models-SEIR model, Morris-Lecar model and the Hodgkin-Huxley model-to show the capability of our proposed method.

To improve prognosis of cancer patients and determine the integrative value for analysis of disease-free survival prediction, a clinic investigation was performed involving with 146 non-small cell lung cancer (NSCLC) patients (83 men and 73 women; mean age: 60.24 years ± 8.637) with a history of surgery. Their computed tomography (CT) radiomics, clinical records, and tumor immune features were firstly obtained and analyzed in this study. Histology and immunohistochemistry were also performed to establish a multimodal nomogram through the fitting model and cross-validation. Finally, Z test and decision curve analysis (DCA) were performed to evaluate and compare the accuracy and difference of each model. In all, seven radiomics features were selected to construct the radiomics score model. The clinicopathological and immunological factors model, including T stage, N stage, microvascular invasion, smoking quantity, family history of cancer, and immunophenotyping. The C-index of the comprehensive nomogram model on the training set and test set was 0.8766 and 0.8426 respectively, which was better than that of the clinicopathological-radiomics model (Z test, P =0.041<0.05), radiomics model and clinicopathological model (Z test, P =0.013<0.05 and P =0.0097<0.05). Integrative nomogram based on computed tomography radiomics, clinical and immunophenotyping can be served as effective imaging biomarker to predict DFS of hepatocellular carcinoma after surgical resection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Dianhui Xiu et al.)

Background: Hepatitis E virus (HEV) infection has become a global concern, especially in pregnant women. However, the association between HEV prevalence and age, gravidity and parity of pregnant women remains unclear., Methods: Pregnant women (n=19,762) were enrolled for HEV prevalence and associated adverse pregnancy outcomes investigation in Qujing City, Yunnan Province of China from May 2019 to December 2020., Results: The seroprevalence of HEV was 11.6% (2,297/19,762; 95% CI:11.2%-12.1%). About 11.4% (2,247/19,762; 95% CI:10.9%-11.8%) were positive for anti-HEV IgG antibody, 0.1% (22/19,762; 95% CI:0.1%-0.2%) were positive for anti-HEV IgM antibody, and 0.1% (28/19,762; 95% CI:0.1%-0.2%) were positive for both anti-HEV IgM and IgG antibodies. Sixty-one out of 2,297 anti-HEV-antibodies-positive pregnant women were positive for HEV RNA. Phylogenetic analysis revealed that all HEV isolates from pregnant women belong to genotype 4. Age, gravidity and parity are associated with increased prevalence of HEV. Pregnant women positive for HEV-IgG antibody bear a higher risk for an adverse pregnancy history and liver injury with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than anti-HEV-negative pregnant women. Furthermore, seropositive pregnant women suffered a higher adverse maternal outcomes risk (crude odds ratio [cOR]=1.29; 95% CI: 1.16-1.43; adjusted odds ratio [aOR]=1.40, 95% CI: 1.25-1.55 for anti-HEV-IgG-positive pregnant women and cOR=1.38, 95% CI: 1.02-1.86; aOR=1.43, 95% CI: 1.05-1.95 for anti-HEV-IgM-positive pregnant women) and fetal outcomes risk (cOR=1.80, 95% CI: 1.61-2.01; aOR=1.77, 95% CI: 1.57-1.99) than anti-HEV-negative pregnant women. Adverse pregnancy outcomes of HEV infection are aggravated by age, gravidity and parity., Conclusion: In this study, we demonstrated high prevalence of HEV in pregnancy women in China, and HEV infection can cause various adverse maternal and neonatal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background & Aims: Tumor-initiating cells (TICs) drive pancreatic cancer tumorigenesis, therapeutic resistance, and metastasis. However, TICs are highly plastic and heterogenous, which impede the robust identification and targeted therapy of such a population. The aim of this study is to identify the surface marker and therapeutic target for pancreatic TICs., Methods: We isolated voltage-gated calcium channel α2δ1 subunit (isoform 5)-positive subpopulation from pancreatic cancer cell lines and freshly resected primary tissues by fluorescence-activated cell sorting and evaluated their TIC properties by spheroid formation and tumorigenic assays. Coimmunoprecipitation was used to identify the direct substrate of CaMKⅡδ., Results: We demonstrate that the voltage-gated calcium channel α2δ1 subunit (isoform 5) marks a subpopulation of pancreatic TICs with the highest TIC frequency among the known pancreatic TIC markers tested. Furthermore, α2δ1 is functionally sufficient and indispensable to promote TIC properties by mediating Ca 2+ influx, which activates CaMKⅡδ to directly phosphorylate PKM2 at T454 that results in subsequent phosphorylation at Y105 to translocate into nucleus, enhancing the stem-like properties. Interestingly, blocking α2δ1 with its specific antibody has remarkably therapeutic effects on pancreatic cancer xenografts by reducing TICs., Conclusions: α2δ1 promotes pancreatic TIC properties through sequential phosphorylation of PKM2 mediated by CaMKⅡδ, and targeting α2δ1 provides a therapeutic strategy against TICs for pancreatic cancer., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Zhijin County is a typical mineral resource-based city in Southwest China. The problem of heavy metals (HM) in the soil in Zhijin County must be considered during regional economic and ecological development. A total of 2436 soil samples (0‒20 cm depth) were collected to analyze the soil pH, organic matter content, and HM spatial distribution and sources. The HM concentrations in the surface soil were found to be higher than the national surface soil background values. Absolute principal component sore-multivariate linear regression (APCS-MLR) showed that the HM sources in the surface soil of Zhijin County were industrial and agricultural activities (48.09%), natural sources (34.47%), and atmospheric deposition (17.43%); 65.53% of HM were produced by anthropogenic activities, which were mainly associated with the mineral industry. The impact of anthropogenic pollution decreased in the following order: paddy field (66.45%) > rainfed cropland (65.91%) > barren land (61.98%) > garden land (61.82%) > forest land (59.11%) > grassland (53.31%). The potential ecological risk of surface soil is moderate, while low-risk areas were mainly distributed in mountainous regions in the north, southwest, and east. The study emphasizes the source and risk assessment of HM in the surface soil of Zhijin County. The results can be used for environmental management planning, decision-making, and risk assessment., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: There is little evidence regarding the optimal surgical sequence for colorectal cancer liver metastasis (CRLM) patients undergoing colorectal resection with simultaneous liver metastasis resection., Methods: CRLM patients from five centers were retrospectively evaluated. The short-term outcomes included intraoperative and postoperative outcomes. Postoperative complications were measured according to the Clavien-Dindo classification. Grade I to II complications were defined as minor postoperative complications. The long-term outcomes were progression-free survival (PFS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to overcome the selection bias between colorectal resection first and liver resection first., Results: A total of 1255 CRLM patients were included. In the multivariable logistic regression analysis, a body mass index (BMI) < 24 kg/m 2 , primary site in the left hemicolon, non-bilobar distribution of liver metastases and no preoperative chemotherapy were significantly associated with the likelihood of colorectal resection first. After 1:1 PSM, there was no significant difference between the colorectal resection first group and the liver resection first group. Compared with patients with colorectal resection first, patients with liver resection first had a comparable postoperative infection rate (15.0% vs. 16.0%, P = 0.735), a longer operation time (305.0 [231.3-416.0] vs. 300.0 [225.0-374.0], P = 0.033), more intraoperative blood loss (200.0 [150.0-400.0] vs. 100.0 [100.0-300.0], P < 0.001), a higher postoperative minor complication rate (28.7% vs. 20.7%, P = 0.023) and a higher postoperative ICU rate (14.7% vs. 8.7%, P = 0.022). IPTW-adjusted Kaplan-Meier analysis showed that patients who underwent colorectal resection first had a similar PFS (P = 0.702, median: 20.6 months vs. 16.6 months) and unfavourable OS (P = 0.014, median: 48.5 months vs. 67.0 months) compared with patients who underwent liver resection first. In the IPTW-adjusted Cox proportional hazards regression analysis, colorectal resection first was an unfavourable risk factor for OS (hazard ratio [HR] = 1.301, 95% CI 1.048-1.616, P = 0.017) and was not an independent predictor for PFS (HR = 0.986, 95% CI 0.831-1.170, P = 0.874). IPTW-adjusted Cox proportional hazards regression analysis, including postoperative complications, operation time, intraoperative blood loss and postoperative chemotherapy, produced consistent results., Conclusion: Although violating the "sterility principle", patients who underwent colorectal resection first did not have an increased postoperative infection rate and had some better short-term outcomes and comparable PFS than those who underwent liver resection first., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) has been proven to improve R0 resection and lymph harvest in treating patients with distal pancreatic cancer. The development of minimally invasive surgery has advantages in postoperative recovery. Therefore, minimally invasive (MI-) RAMPS may combine the advantages of both benefits to improve survival. Nevertheless, evidence to validate the safety and efficacy of MI-RAMPS is limited., Method/design: The MIRROR trial will be the first multicenter prospective randomized clinical trial to investigate the outcome of MI-RAMPS. The hypothesis is that MI-RAMPS is superior in postoperative recovery. The primary outcome is the length of postoperative stay. Based on the hypothesis and primary outcome, the sample size is 250 patients (125 participants in each group). The trial will investigate factors related to surgical safety, short-term outcome, pathological assessment, and survival as secondary outcomes., Conclusion: This study will offer a relatively higher level of evidence to further illustrate the accessibility and benefits of MI-RAMPS for the treatment of distal pancreatic cancer., Clinical Trial Registration: Clinicaltrials.gov, NCT03770559., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Zhang, Yang, Xiu, Peng, Sun, Cao, Wu, Wang, Yuan, Chen, Wang, Tian, Wang, Liu, Xu, Liu, Zhao and MIRROR study group.)

Background: Bilateral hepatolithiasis is an intractable disease and repeated attacks of acute cholangitis seriously threaten patient health. The surgical approaches evolve along with gradually greater understanding of its pathophysiology., Methods: This is a retrospective cohort study for bilateral hepatolithiasis from January 1958 to December 2018. Before May 1993 (Group A, n = 70), three surgical approaches were adopted: 37 patients with common bile duct exploration (CBDE), 29 with choledochoenterostomy (CE) and four with partial hepatectomy (PH). After June 1993 (Group B, n = 150), 101 patients underwent Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), and 16 with CBDE, 21 with CE, 12 with PH. The perioperative and long-term outcomes were compared., Results: After 1993, the cholangitis recurrence rate significantly decreased from 49.2% to 20.9%, and the stone recurrence rate from 76.3% to 37.1% (both P < .001). Also, the stone-/cholangitis-free durations were prolonged significantly (median: 50.8 vs 26.4/49.6 vs 16.2 months, both P < .001). Preoperative cholangitis was an independent risk factor for stone recurrence (hazard ratio [HR] = 1.863, P = .018), and residual stone for cholangitis recurrence (HR = 2.838, P < .001). OSPCHS and PH were protective surgical approaches for recurrent stone (CBDE: reference; OSPCHS: HR = .469, P = .016, PH: HR = .219, P = .018) and cholangitis (CBDE: reference; OSPCHS: HR = .421, P = .010, PH: HR = .283, P = .093)., Conclusions: For bilateral hepatolithiasis, the management should focus on hepatobiliary lesion eradication and Oddi sphincter function preservation., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Magnetic resonance imaging (MRI) has been shown to be associated with prognosis in some tumors; however, the correlation in pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. In this retrospective study, we ultimately included 136 patients and analyzed quantitative MRI parameters that are associated with prognosis and recurrence patterns in PDAC using survival analysis and competing risks models; all the patients have been operated on with histopathology and immunohistochemical staining for further evaluation. In intravoxel incoherent motion diffusion-weighted imaging (DWI), we found that pure-diffusion coefficient D value was an independent risk factor for overall survival (OS) (HR: 1.696, 95% CI: 1.003-2.869, p = 0.049) and recurrence-free survival (RFS) (HR: 2.066, 95% CI: 1.252-3.409, p = 0.005). A low D value (≤1.08 × 10 -3 mm 2 /s) was significantly associated with a higher risk of local recurrence (SHR: 5.905, 95% CI: 2.107-16.458, p = 0.001). Subgroup analysis revealed that patients with high D and f values had significantly better outcomes with adjuvant chemotherapy. Distant recurrence patients in the high-D value group who received chemotherapy may significantly improve their OS and RFS. It was found that preoperative multiparametric quantitative MRI correlates with prognosis and recurrence patterns in PDAC. Diffusion coefficient D value can be used as a noninvasive biomarker for predicting prognosis and recurrence patterns in PDAC.

In this work, a designed porous DNA crystal with high intrinsic biocompatibility was used as the scaffold material to load fluorescent guest molecules to detect anti-cancer drugs. It is shown here that the synthesized crystals have the characteristics consistent with the designed large solvent channels, and can therefore accommodate guest molecules such as fluorescent proteins that cannot be accommodated by less porous crystals. Eu(TTA) 3 phen and Tb(acac) 3 phen lanthanide complexes were individually noncovalently loaded into the porous crystals, resulting in hybrid luminescent DNA crystals. Emodin, an anti-cancer, anti-tumor, anti-inflammatory drug, was found to quench lanthanide complexes in solution or in crystals. Notably, emodin is the active ingredient of Lianhua Qingwen Capsule, an anti-COVID-19 drug candidate. Therefore, the porous DNA crystals reported here have potential applications as a biocompatible and theranostic delivery biomaterial for functional macromolecules.

Background: Neuroendocrine tumors (NETs) are a group of heterogenous tumors originating from neuroendocrine system. Approximately, 40 percent will go through liver metastases, and liver-directed therapy was proved to improve the survival outcome. Parenchyma-sparing hepatectomy is advocated for the resection of NETs liver metastases while the possible relatively low negative margin rate is concerned. Indocyanine green (ICG) fluorescence imaging provides a real-time navigation on determination of surgical margins in colorectal cancer liver metastases. However, there was no previous study that reported the applications of ICG fluorescence imaging in NETs liver metastases. The present study aimed to evaluate the feasibility and security of using ICG fluorescence imaging to determine surgical margins of NETs liver metastases during operation., Methods: A retrospective two-arm cohort study was performed on 25 consecutive patients with NETs liver metastases who underwent laparoscopic parenchyma-sparing hepatectomy (LPSH). Patients were divided into two groups according to whether or not the ICG fluorescence imaging was used. Data on sociodemographic characteristics, laboratory parameters, pathology results, and surgical outcomes were collected., Results: A total of 145 tumors pathologically diagnosed with NETs liver metastases were resected from 25 patients. The pathological results indicated negative margins in all tumors (102/102) in LPSH with ICG fluorescence imaging group. The negative margin rate was significantly higher in LPSH using the ICG fluorescence imaging (100% v.s 88.4%, p = 0.002). Surgical outcomes, including operation time, estimated blood loss, intraoperative transfusion rate, and postoperative morbidity, were comparable between LPSH with and without ICG fluorescence imaging groups., Conclusion: ICG fluorescence imaging showed the potential to identify tumor boundaries and determine surgical margins. This technique may serve as a valuable intraoperative navigation in patients with NETs liver metastases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)