Deep learning based digital pathology for predicting treatment response to first-line PD-1 blockade in advanced gastric cancer.

BACKGROUND: Advanced unresectable gastric cancer (GC) patients were previously treated with chemotherapy alone as the first-line therapy. However, with the Food and Drug Administration's (FDA) 2022 approval of programmed cell death protein 1 (PD-1) inhibitor combined with chemotherapy as the first-li ne treatment for advanced unresectable GC, patients have significantly benefited. However, the significant costs and potential adverse effects necessitate precise patient selection. In recent years, the advent of deep learning (DL) has revolutionized the medical field, particularly in predicting tumor treatment responses. Our study utilizes DL to analyze pathological images, aiming to predict first-line PD-1 combined chemotherapy response for advanced-stage GC. METHODS: In this multicenter retrospective analysis, Hematoxylin and Eosin (H&E)-stained slides were collected from advanced GC patients across four medical centers. Treatment response was evaluated according to iRECIST 1.1 criteria after a comprehensive first-line PD-1 immunotherapy combined with chemotherapy. Three DL models were employed in an ensemble approach to create the immune checkpoint inhibitors Response Score (ICIsRS) as a novel histopathological biomarker derived from Whole Slide Images (WSIs). RESULTS: Analyzing 148,181 patches from 313 WSIs of 264 advanced GC patients, the ensemble model exhibited superior predictive accuracy, leading to the creation of ICIsNet. The model demonstrated robust performance across four testing datasets, achieving AUC values of 0.92, 0.95, 0.96, and 1 respectively. The boxplot, constructed from the ICIsRS, reveals statistically significant disparities between the well response and poor response (all p-values < = 0.001). CONCLUSION: ICIsRS, a DL-derived biomarker from WSIs, effectively predicts advanced GC patients' responses to PD-1 combined chemotherapy, offering a novel approach for personalized treatment planning and allowing for more individualized and potentially effective treatment strategies based on a patient's unique response situations.

Digital histopathological images of biopsy predict response to neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been recognized as an effective therapeutic option for locally advanced gastric cancer as it is expected to reduce tumor size, increase the resection rate, and improve overall survival. However, for patients who are not responsive to NAC, the best operation timing may be missed together with suffering from side effects. Therefore, it is paramount to differentiate potential respondents from non-respondents. Histopathological images contain rich and complex data that can be exploited to study cancers. We assessed the ability of a novel deep learning (DL)-based biomarker to predict pathological responses from images of hematoxylin and eosin (H&E)-stained tissue. METHODS: In this multicentre observational study, H&E-stained biopsy sections of patients with gastric cancer were collected from four hospitals. All patients underwent NAC followed by gastrectomy. The Becker tumor regression grading (TRG) system was used to evaluate the pathologic chemotherapy response. Based on H&E-stained slides of biopsies, DL methods (Inception-V3, Xception, EfficientNet-B5, and ensemble CRSNet models) were employed to predict the pathological response by scoring the tumor tissue to obtain a histopathological biomarker, the chemotherapy response score (CRS). The predictive performance of the CRSNet was evaluated. RESULTS: 69,564 patches from 230 whole-slide images of 213 patients with gastric cancer were obtained in this study. Based on the F1 score and area under the curve (AUC), an optimal model was finally chosen, named the CRSNet model. Using the ensemble CRSNet model, the response score derived from H&E staining images reached an AUC of 0.936 in the internal test cohort and 0.923 in the external validation cohort for predicting pathological response. The CRS of major responders was significantly higher than that of minor responders in both internal and external test cohorts (both p < 0.001). CONCLUSION: In this study, the proposed DL-based biomarker (CRSNet model) derived from histopathological images of the biopsy showed potential as a clinical aid for predicting the response to NAC in patients with locally advanced GC. Therefore, the CRSNet model provides a novel tool for the individualized management of locally advanced gastric cancer.

HSP70 promotes tumor progression by stabilizing Skp2 expression in gastric cancer cells.

Gastric cancer (GC) has one of the highest tumor incidences worldwide. Heat shock protein 70 (HSP70) is highly expressed and plays a critical role in the occurrence, progression, metastasis, poor prognosis, and drug resistance of GC. However, the underlying mechanisms of HSP70 are not clear. To explore the regulatory role of HSP70 in GC, we performed cell counting kit-8 (CCK-8) and EdU staining assays to assess cell proliferation; immunohistochemistry and western blot analyses to assess protein expression; coimmunoprecipitation (Co-IP) assays to assess interactions between two proteins; and immunofluorescence to assess protein expression and localization. HSP70 was highly expressed in clinical samples from patients with GC and indicated a poor prognosis. HSP70 inhibition enhanced the sensitivity of GC cells to thermochemotherapy. Furthermore, we found that S phase kinase-associated protein 2 (Skp2) was highly expressed in GC and correlated with HSP70 in array data from The Cancer Genome Atlas (TCGA). Importantly, HSP70 inhibition promoted Skp2 degradation. Skp2 overexpression abrogated HSP70 inhibition-induced cell cycle arrest, suggesting that the role of HSP70 in GC depends on Skp2 expression. Our results illustrate a possible regulatory mechanism of HSP70 and may provide a therapeutic strategy for overcoming resistance to thermochemotherapy.

Differentiation of small (≤ 3 cm) hepatocellular carcinomas from benign nodules in cirrhotic liver: the added additive value of MRI-based radiomics analysis to LI-RADS version 2018 algorithm.

BACKGROUND: Accurate characterization of small nodules in a cirrhotic liver is challenging. We aimed to determine the additive value of MRI-based radiomics analysis to Liver Imaging Reporting and Data System version 2018 (LI-RADS v 2018) algorithm in differentiating small (≤ 3 cm) hepatocellular carcinomas (HCCs) from benign nodules in cirrhotic liver. METHODS: In this retrospective study, 150 cirrhosis patients with histopathologically confirmed small liver nodules (HCC, 112; benign nodules, 44) were evaluated from January 2013 to October 2018. Based on the LI-RADS algorithm, a LI-RADS category was assigned for each lesion. A radiomics signature was generated based on texture features extracted from T1-weighted, T2W, and apparent diffusion coefficient (ADC) images by using the least absolute shrinkage and selection operator regression model. A nomogram model was developed for the combined diagnosis. Diagnostic performance was assessed using receiver operating characteristic curve (ROC) analysis. RESULTS: A radiomics signature consisting of eight features was significantly associated with the differentiation of HCCs from benign nodules. Both LI-RADS algorithm (area under ROC [Az] = 0.898) and the MRI-Based radiomics signature (Az = 0.917) demonstrated good discrimination, and the nomogram model showed a superior classification performance (Az = 0.975). Compared with LI-RADS alone, the combined approach significantly improved the specificity (97.7% vs 81.8%, p = 0.030) and positive predictive value (99.1% vs 92.9%, p = 0.031) and afforded comparable sensitivity (97.3% vs 93.8%, p = 0.215) and negative predictive value (93.5% vs 83.7%, p = 0.188). CONCLUSIONS: MRI-based radiomics analysis showed additive value to the LI-RADS v 2018 algorithm for differentiating small HCCs from benign nodules in the cirrhotic liver.

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy.

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study.

OBJECTIVE: Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM. METHODS: This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias. RESULTS: Of 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58-0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%-14.8%) and 18.4% (95% CI, 12.3%-24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months. CONCLUSIONS: Compared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.

From Detection to Resection: Photoacoustic Tomography and Surgery Guidance with Indocyanine Green Loaded Gold Nanorod@liposome Core-Shell Nanoparticles in Liver Cancer.

Conventional imaging methods encounter challenges in diagnosing liver cancer that is less than 10 mm or without typical hypervascular features. With deep penetration and high spatial resolution imaging capability, the emerging photoacoustic tomography may offer better diagnostic efficacy for noninvasive liver cancer detection. Moreover, near-infrared fluorescence imaging-guided hepatectomy was proven to be able to identify nodules at the millimeter level. Thus, suitable photoacoustic and fluorescence dual-modality imaging probe may benefit patients in early diagnosis and complete resection. In this study, we fabricated indocyanine green loaded gold nanorod@liposome core-shell nanoparticles (Au@liposome-ICG) to integrate both imaging strategies. These nanoparticles exhibit superior biocompatibility, high stability, and enhanced dual-model imaging signals. Next, we explored their effectiveness of tumor detection and surgery guidance in orthotopic liver cancer mouse models. Histological analysis confirmed the accuracy of the probe in liver cancer detection and resection. This novel dual-modality nanoprobe holds promise for early diagnosis and better surgical outcome of liver cancer and has great potential for clinical translation.

Individualized preoperative planning using three-dimensional modeling for Bismuth and Corlette type III hilar cholangiocarcinoma.

BACKGROUND: A detailed evaluation of blood supply anatomy, especially the biliary anatomy at the hepatic hilus, is essential to ensure a complete and curative resection for Bismuth and Corlette type III hilar cholangiocarcinoma. The study aimed to investigate the impact of individualized preoperative planning using 3D modeling on surgical treatment for type III hilar cholangiocarcinoma. METHODS: This was a retrospective study of patients with type III hilar cholangiocarcinoma (n=47) who underwent surgery at the Hepatobiliary Surgery Department of Zhujiang Hospital between March 2007 and January 2015. All patients had undergone preoperative computed tomography (CT) examination, and 3D images were reconstructed. Preoperative surgery simulation was performed, and the simulation was applied in the subsequent surgery. Clinical, surgical, and pathological characteristics were compared between patients undergoing preoperative planning (n=25) and those who did not (n=22). Complications were examined. RESULTS: Surgical time and blood loss were significantly smaller in patients with 3D reconstruction compared to those without. The number of bile duct orifices was correctly estimated in 14/25 (56.0%) patients with preoperative planning. The width of the hepatic surgical margin could be measured for 18 hepatic ducts, and 17 (68.0%) of them were pathologically diagnosed as margin-negative. CONCLUSIONS: This technique has the advantages of precise visualization of the anatomic structures and 3D assessment of biliary branches and vessels, allowing improved operative planning for the treatment of hilar cholangiocarcinoma.

GP73 is down-regulated in gastric cancer and associated with tumor differentiation.

BACKGROUND: Golgi protein 73 (GP73) is a type II Golgi transmembrane protein. It is over-expressed in several cancers, including hepatocellular carcinomas, bile duct carcinomas, lung cancer and prostate cancer. However, there are few reports of GP73 in gastric cancer. This study is aimed at investigating the expression of GP73 and its relationship with clinical pathological characters in gastric cancer. METHODS: GP73 mRNA level was determined by quantitative real-time RT-PCR in 41 pairs of matched gastric tumorous tissues and adjacent non-tumorous mucosal tissues. Western blotting was also performed to detect the GP73 protein level. GP73 protein expression was analyzed by immunohistochemistry in 52 clinically characterized gastric cancer patients and 10 non-tumorous gastric mucosal tissue controls. RESULTS: The mRNA and protein level of GP73 were significantly down-regulated in gastric tumorous tissues compared with the non-tumorous mucosal tissues. In non-tumorous mucosa, strong diffuse cytoplasmic staining can be seen in cells located at the surface of the glandular and foveolar compartment; while in tumorous tissues, the staining was much weaker or even absent, and mainly in a semi-granular dot-like staining pattern. The expression level of GP73 protein was associated with patients' gender and tumor differentiation. CONCLUSIONS: GP73 was normally expressed in non-tumorous gastric mucosa and down-regulated in gastric cancer. Its expression in gastric cancer was correlated with tumor differentiation.

Seasonal shift in gut microbiome diversity in wild Sichuan takin (Budorcas tibetanus) and environmental adaptation.

In this study, we investigated the change in microbiome composition of wild Sichuan takin (Budorcas tibetanus) during winter and spring and analyzed the physiological implications for such changes. Diversity analyses of the microbiome (average 15,091 high-quality reads per sample) in 24 fecal samples (15 from winter, 9 from spring) revealed that spring samples had higher species diversity and were compositionally different from winter samples (P < 0.05). Taxonomic composition analysis showed that the relative abundance increased in spring for Patescibacteria (2.7% vs. 0.9% in winter, P < 0.001) and Tenericutes (1.9% vs. 1% in winter, P < 0.05). Substantial increases in relative abundance of Ruminococcaceae and Micrococcaceae were identified in spring and winter, respectively. Mann-Whitney U and ANCOM identified seven differentially abundant genera: Enterococcus, Acetitomaculum, Blautia, Coprococcus 1, Lachnospiraceae UCG 008, Ruminococcus 2 and Ralstonia. All seven genera were significantly more abundant in spring (average 0.016-1.2%) than winter (average 0-0.16%), with the largest difference found in Ruminococcus (1.21% in spring vs. 0.16% in winter). The other six genera were undetectable in winter. Functional prediction and pathway analysis revealed that biosynthesis of cofactors (ko01240) had the highest gene count ratios in the winter, followed by the two-component system (ko02020). Seasonal variation affects the gut microbiomes in wild Sichuan takins, with winter associated with lower species diversity and spring with enrichment of cellulose-degrading genera and phytopathogens. Such changes were crucial in their adaptation to the environment, particularly the difference in food abundance.

Vessels that encapsulate tumor clusters (VETC) pattern predicts the efficacy of adjuvant TACE in hepatocellular carcinoma.

PURPOSE: Postoperative adjuvant trans-catheter arterial chemoembolization (TACE) is regarded as a common strategy for hepatocellular carcinoma (HCC) patients at a high risk of recurrence. However, there are currently no clinically available biomarkers to predict adjuvant TACE response. Vessels that encapsulate tumor clusters (VETC) can be used as an independent predictor of HCC prognosis. In this study, we aimed to explore whether the VETC pattern could predict adjuvant TACE benefit. METHODS: Vascular pattern and HIF-1α expression were detected in immunohistochemistry. The survival benefit of adjuvant TACE therapy for patients with or without VETC pattern (VETC+ /VETC-) was evaluated. RESULTS: The adjuvant TACE therapy obviously improved the TTR and OS in VETC+ patients, while adjuvant TACE therapy could not benefit from VETC- patients. Univariate and multivariate analysis revealed that adjuvant TACE therapy significantly improved the TTR and OS in VETC+ patients, but not in VETC- patients. In addition, the VETC+ , but not VETC- , patients could benefit from adjuvant TACE therapy in patients with high-risk factors of vascular invasion, larger tumor or multiple tumor. The mechanistic investigations revealed that the favorable efficacy of adjuvant TACE on VETC+ patients, but not VETC- ones, may be not due to the activation of HIF-1α pathway. CONCLUSION: The VETC pattern may represent a novel and reliable factor for selecting HCC patients who may benefit from adjuvant TACE therapy, and the combination of VETC pattern and tumor characteristics may help stratify patients' outcomes and responses to adjuvant TACE therapy.

REG4 contributes to the invasiveness of pancreatic cancer by upregulating MMP-7 and MMP-9.

Recent studies have shown that overexpression of regenerating gene family member 4 (REG4) is associated with the initiation and progression of pancreatic cancer. In our study, we explored the role of REG4 in the invasion of pancreatic cancer. Real-time PCR and Western blot analysis were used to determine REG4 expression in pancreatic cancer cell lines. An MTT assay was carried out to test the effect of REG4 on the growth of pancreatic cancer cells. The involvement of REG4 in cancer cell invasion was examined by Transwell invasion assay. Two MMPs, MMP-7 and MMP-9, were identified from a pool of candidate genes as being related to REG4-induced cell invasion by PCR and Western blotting. Immunohistochemistry was used to confirm the correlation between REG4 and the two MMPs. High expression of REG4 was found in BXPC-3 cells and its culture media. But in PANC-1 and ASPC-1 cell lines, REG4 expression levels were very low, and no detectable protein was found in the culture medium. The MTT and Transwell invasion assays showed that recombinant REG4 protein and BXPC-3 conditioned media significantly promoted the proliferation and invasiveness of pancreatic cancer cells. It was also shown that MMP-7 and MMP-9 are upregulated by REG4 induction using real-time PCR and Western blotting analysis. Immunohistochemical study further verified this result. In conclusion, REG4 promotes not only growth but also in vitro invasiveness of pancreatic cancer cells by upregulating MMP-7 and MMP-9.

Added Value of Quantitative Apparent Diffusion Coefficients for Identifying Small Hepatocellular Carcinoma from Benign Nodule Categorized as LI-RADS 3 and 4 in Cirrhosis.

BACKGROUND AND AIMS: Correct identification of small hepatocellular carcinomas (HCCs) and benign nodules in cirrhosis remains challenging, quantitative apparent diffusion coefficients (ADCs) have shown potential value in characterization of benign and malignant liver lesions. We aimed to explore the added value of ADCs in the identification of small (≤3 cm) HCCs and benign nodules categorized as Liver Imaging Reporting and Data System (LI-RADS) 3 (LR-3) and 4 (LR-4) in cirrhosis. METHODS: Ninety-seven cirrhosis patients with 109 small nodules (70 HCCs, 39 benign nodules) of LR-3 and 4 LR-4 based on major and ancillary magnetic resonance imaging features were included. Multiparametric quantitative ADCs of the lesions, including the mean ADC (ADCmean), minimum ADC (ADCmin), maximal ADC (ADCmax), ADC standard deviation (ADCstd), and mean ADC value ratio of lesion-to-liver parenchyma (ADCratio) were calculated. Regarding the joint diagnosis, a nomogram model was plotted using multivariate logistic regression analysis. The performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: The ADCmean, ADCmin, ADCratio, and ADCstd were significantly associated with the identification of small HCC and benign nodules (p<0.001). For the joint diagnosis, the LI-RADS category (odds ratio [OR]=12.50), ADCmin (OR=0.14), and ADCratio (OR=0.12) were identified as independent factors for distinguishing HCCs from benign nodules. The joint nomogram model showed good calibration and discrimination, with a C-index of 0.947. Compared with the LI-RADS category alone, this nomogram model demonstrated a significant improvement in diagnostic performance, with AUC increasing from 0.820 to 0.967 (p=0.001). CONCLUSIONS: The addition of quantitative ADCs could improve the identification of small HCC and benign nodules categorized as LR-3 and 4 LR-4 in patients with cirrhosis.

Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy.

Background: Gastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC. Methods: Biomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study. Results: The tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan-Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts. Conclusion: We found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.

Engineering the Redox-Driven Channel for Precisely Regulating Nanoconfined Glutathione Identification and Transport.

Bioinspired artificial nanochannels for molecular and ionic transport have extensive applications. However, it is still a huge challenge to achieve an intelligent transport system with high selectivity/efficiency and controllability. Inspired by glutathione transport across the plasma membrane via redox regulation, we herein designed and fabricated a redox-reactive artificial nanochannel based on the host-guest chemical strategy. The nanochannel platform achieved high selectivity/efficiency for the identification and transmission of glutathione in the confined space. In addition, this nanochannel can switch between the ON and OFF states through the redox reaction. This redox-regulated system can provide a potential application for detection/binding of biological analytes and redox-controlled drug release.

MicroRNA-124-3p inhibited progression of nasopharyngeal carcinoma by interaction with PCDH8 and the inactivation of PI3K/AKT/mTOR pathway.

Nasopharyngeal carcinoma (NPC) is characterised by distinct geographical distribution and is particularly prevalent in Asian countries. But the mechanisms related to the progression of nasopharyngeal carcinoma (NPC) are not completely understood. MiR-124-3p functions as a tumor suppressor in many kinds of human cancers. Here, we explored the effects and mechanism of miR-124-3p on the proliferation and colony formation in NPC. In our study, we reported that miR-124-3p was significantly downregulated in NPC tissues and cell lines. Overexpression miR-124-3p decreased NPC cell proliferation and colony formation abilities. Meanwhile, knockdown miR-124-3p increased proliferation and colony formation abilities. Additionally, dual-luciferase assay showed that miR-124-3p could positively regulated PCDH8 by targeting its 3'-UTR. Overexpression of PCDH8 could partially rescue the proliferation and colony formation role of miR-124-3p inhibitor. Our study indicated that miR-124-3p played a tumor suppressor by directly interacting with PCDH8 and inhibiting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Overall, we found that miR-124-3p inhibited the activation of the PI3K/AKT/mTOR signaling pathway in NPC by interacting with PCDH8. Thus, PCDH8 may be a potential molecular target that impeded NPC proliferation and colony formation.

Assessment of effective conservation of the Sichuan takin by giant panda reserves through functional zoning.

The flagship species conservation strategy is widely practiced in nature reserves. However, few studies have quantitatively explored whether the current functional zoning adequately conserves the habitats of other species. To examine this problem, we selected the Tangjiahe, Xuebaoding, and Wanglang national nature reserves in southwest China and tested the protective efficiency of the giant panda (Ailuropoda melanoleuca) reserves on a local herbivore-Sichuan takin (Budorcas taxicolor tibetana) in functional zoning. We predicted that the habitat distribution of the Sichuan takin with Maxent and habitat suitability would be classified as very low, low, moderately, or highly suitable. We calculated the percentage of each type of habitat class across the core, buffer, and experimental zones in these reserves and introduced an economic index present value index to further assess the efficacy of the functional zoning in conserving the habitat of Sichuan takin. Our findings indicate that suitable habitat distributions of Sichuan takin are multicore and influenced by diverse variables in different nature reserves. The percentage of moderately suitable and highly suitable habitat in the core zone is 69% and 54% in Tangjiahe, 76% and 75% in Wanglang, and 47% and 28% in Xuebaoding, respectively. The present value index of moderately and highly suitable habitat is 1.01 and 0.79 (Tangjiahe), 0.87 and 0.86 (Wanglang), 0.76 and 0.44 (Xuebaoding), respectively. The efficiency of functional zoning on Sichuan takin seems lower than imagined in giant panda reserves, and species that have important impacts on local ecosystem need further estimation and greater focus.

Evaluation of Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Stage III Epithelial Ovarian Cancer.

Importance: Interval cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising oncologic outcomes for patients with advanced ovarian cancer, but a large-scale, multicenter study to evaluate the efficacy of HIPEC combined with primary cytoreductive surgery (PCS) has yet to be conducted. Objective: To compare survival outcomes between PCS with HIPEC vs PCS alone for patients with stage III epithelial ovarian cancer. Design, Setting, and Participants: This cohort study was conducted from January 2010 to May 2017 at 5 high-volume institutions in China. A total of 584 patients with stage III primary epithelial ovarian cancer were treated with either PCS alone or PCS with HIPEC. The median (interquartile range) follow-up period was 42.2 (33.3-51.0) months. Data analysis was conducted from August to December 2019. Exposures: PCS with HIPEC vs PCS alone. Main Outcomes and Measures: Primary outcomes were median survival time and 3-year overall survival. The inverse probability of treatment weighting (IPTW) method, based on propensity score, was used to control for confounding factors. Results: From a total of 789 patients with stage III epithelial ovarian cancer, 584 patients (74.0%; mean [SD] age, 55.0 [10.5] years) were ultimately included for IPTW in this study. Of the 584 patients, 425 (72.8%) underwent PCS with HIPEC and 159 (27.2%) underwent PCS alone. After IPTW adjustment, the median survival time was 49.8 (95% CI, 45.2-60.2) months for patients undergoing PCS with HIPEC and 34.0 (95% CI, 28.9-41.5) months for patients undergoing PCS alone, and the 3-year overall survival rate was 60.3% (95% CI, 55.3%-65.0%) for patients undergoing PCS with HIPEC and 49.5% (95% CI, 41.0%-57.4%) for patients undergoing PCS alone (weighted hazard ratio, 0.64; 95% CI, 0.50-0.82; P < .001). Further stratified into complete and incomplete surgery subgroups, patients in the PCS with HIPEC group had significantly better survival than those in the PCS group, except for the 3-year overall survival rate in the incomplete subgroup. Among those who underwent complete surgical procedures and comparing those who received PCS with HIPEC vs those who received PCS alone, the median survival time was 53.9 (95% CI, 46.6-63.7) months vs 42.3 (95% CI, 31.1-59.3) months (P = .02), and the 3-year overall survival rate was 65.9% (95% CI, 60.1%-71.2%) vs 55.4% (95% CI, 44.7%-64.8%) (P = .04); meanwhile, among patients who underwent incomplete surgical procedures and comparing those who received PCS with HIPEC vs those who received PCS alone, the median survival time was 29.2 (95% CI, 22.3-45.5) months vs 19.9 (95% CI, 11.6-39.1) months (P = .03), and the 3-year OS rate was 44.3% (95% CI, 34.6%-53.4%) vs 36.7% (95% CI, 23.4%-50.1%) (P = .19). The treatment was well tolerated in both groups. Conclusions and Relevance: In this study, the PCS with HIPEC treatment approach was associated with better long-term survival. When complete PCS is possible, this approach could be a valuable therapy for patients with stage III epithelial ovarian cancer.

Near infrared-emitting persistent luminescent nanoparticles for Hepatocellular Carcinoma imaging and luminescence-guided surgery.

Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, is increasing nowadays and poses a serious threat to human health. However, if treated effectively and timely, it is clinically manageable or curable. Therefore, accurate detection and complete surgical resection remain priorities for HCC with a high potential of improving both survival and quality of life. Lacking of real-time guide technology, traditional surgery are usually relied on the subjective experience of surgeon, which have the limitation of high sensitivity detection tumor. Here, we developed a contrast agent, ZnGa2O4Cr0.004 (ZGC), used for guided surgery during operation to accurate delineation of HCC. ZGC showed excellent long-lasting afterglow properties that lasted for hours, which can aid in real-time guided surgery. Meanwhile, ZGC display high spatial resolution and deep penetration during pre-operation for diagnostic computed tomography (CT). Interestingly, we observed reverse imaging in the tumor region, known as a "dark hole", which further improves the contrast for surgery. This new multi-modality nanoparticle has great potential for accurate liver cancer imaging and resection guidance.

Metagenomic analysis of Sichuan takin fecal sample viromes reveals novel enterovirus and astrovirus.

The Sichuan takin inhabits the bamboo forests in the Eastern Himalayas and is considered as a national treasure of China with the highest legal protection and conservation status considered as vulnerable according to The IUCN Red List of Threatened Species. In this study, fecal samples of 71 Sichuan takins were pooled and deep sequenced. Among the 103,553 viral sequences, 21,961 were assigned to mammalian viruses. De novo assembly revealed genomes of an enterovirus and an astrovirus and contigs of circoviruses and genogroup I picobirnaviruses. Complete genome sequencing and phylogenetic analysis showed that Sichuan takin enterovirus is a novel serotype/genotype of the species Enterovirus G, with evidence of recombination. Sichuan takin astrovirus is a new subtype of bovine astrovirus, probably belonging to a new genogroup in the genus Mamastrovirus. Further studies will reveal whether these viruses can also be found in Mishmi takin and Shaanxi takin and their pathogenic potentials.