A whole-slide foundation model for digital pathology from real-world data.

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.

Clinicopathological features and prognostic value of CD276 expression in female reproductive system malignancies: A meta-analysis.

The relationship between CD276 and malignancies of the female reproductive system has previously been controversial. The purpose of this study was to evaluate the predictive value of CD276 expression in clinicopathological features and prognosis of female reproductive system malignant tumors through meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang databases were searched for studies published up to December 2022 on the role of CD276 expression in the clinicopathological features and prognosis of female reproductive system malignancies. STATA 14.0 was used for meta-analysis. A total of 10 studies were included, involving 840 patients with malignant tumors of the female reproductive system. The results showed that in terms of clinicopathological features: CD276 expression was closely related to lymph node status [OR = 2.33， 95 %CI = 1.32-4.11， P = 0.003], tumor differentiation [OR = 2.15， 95 %CI = 1.27-3.63, P = 0.004], and FIGO stage [OR = 2.58， 95 %CI = 1.44-4.61, P = 0.001] of reproductive system malignant tumors. In terms of prognosis: CD276 expression is strongly associated with shorter OS in patients with female reproductive system malignancies [HR = 3.33, 95 % CI = 1.36-8.15, P = 0.01]. CD276 may be a new target for immunotherapy and a biomarker for predicting poor prognosis of female reproductive system malignancies.

Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia. We determined that CRC patients resistant to bevacizumab treatment presented with elevated levels of histone lactylation and inhibition of histone lactylation efficiently suppressed CRC tumorigenesis, progression and survival in hypoxia. Histone lactylation promoted the transcription of RUBCNL/Pacer, facilitating autophagosome maturation through interacting with BECN1 (beclin 1) and mediating the recruitment and function of the class III phosphatidylinositol 3-kinase complex, which had a crucial role in hypoxic cancer cells proliferation and survival. Moreover, combining inhibition of histone lactylation and macroautophagy/autophagy with bevacizumab treatment demonstrated remarkable treatment efficacy in bevacizumab-resistance patients-derived pre-clinical models. These findings delivered a new exploration and important supplement of metabolic reprogramming-epigenetic regulation, and provided a new strategy for improving clinical efficacy of bevacizumab in CRC by inhibition of histone lactylation.Abbreviations: 2-DG: 2-deoxy-D-glucose; BECN1: beclin 1; CQ: chloroquine; CRC: colorectal cancer; DMOG: dimethyloxalylglycine; H3K18la: histone H3 lysine 18 lactylation; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Nala: sodium lactate; PDO: patient-derived orgnoid; PDX: patient-derived xenograft; RUBCNL/Pacer: rubicon like autophagy enhancer; SQSTM1/p62: sequestosome 1.

The Association of Melanoma-Associated Antigen-C Gene With Clinicopathological Characteristics and Prognosis in Breast Cancer: A Systematic Review and Meta-Analysis.

To investigate the correlation of melanoma-associated antigen-C gene expression with clinicopathologic characteristics and prognosis in patients with breast cancer through a meta-analysis. PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP databases were searched from the establishment of the databases to December 2022. The New castle-Ottawa Scale (NOS) was used for literature quality evaluation, and meta-analysis of all studies was performed using Rev Man 5.3 and Stata14.0. A total of 11 studies and 1146 samples were included in the meta-analysis. High expression of MAGE-C gene was significantly correlated with tumor grade (OR = 8.06, 95%CI:4.14-15.67, P < .00001), lymph node metastasis (OR = 8.06, 95%CI:4.14-15.67, P < .00001), tumor type (OR = 0.36, 95%CI: 0.23-0.49, P < .00001), tumor stage (OR = 0.14, 95%CI: 0.05-0.38, P = .0001<.05), ER expression (OR = 0.14, 95%CI: 0.05-0.38, P = .0001<.05), HER-2 expression (OR = 0.24, 95%CI:0.11-0.57, P = .001<.05) and tumor embolus (OR = 0.24, 95%CI:0.11-0.57, P = .001<.05). In addition, the MAGE-C expression was correlated with the reduced overall survival (HR = 2.13, 95%CI: 1.52-2.99, P < .0001), recurrence-free survival (HR = 2.59, 95%CI:1.47-4.56, P = .0010) and metastasis-free survival (OR = 2.52, 95%CI: 1.38-4.59, P = .003). The high expression of MAGE-C gene is closely related to some clinicopathological parameters and poor prognosis of breast cancer, which may be used as a potential biomarker to determine the prognosis of breast cancer.

Risk factors for cervical lymph node metastasis in the central or lateral cervical region in medullary thyroid carcinoma: a systematic review and meta-analysis.

PURPOSE: Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC. METHODS: The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software. RESULTS: A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001). CONCLUSION: Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients.

Identification and analysis of methylation signature genes and association with immune infiltration in pediatric acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a common leukemia with low cure rate and poor prognosis among pediatric patients. The regulation of AML immune microenvironment and methylation remains to be explored. Pediatric and adult AML patients differ significantly in epigenetic factors, and the efficiency of treatment modalities varies between the two groups of patients. METHODS: We collected mRNA, miRNA and DNA methylation data from pediatric AML patients across multiple databases. Differentially expression genes were identified, and a gene-miRNA regulatory network was constructed. Prognostic risk models were established by integrating LASSO and Cox regression, and a nomogram was generated. Based on this model, we investigated tumor-infiltrating immune cells and cell communication, analyzing the biological functions and pathways associated with prognostic factors. Furthermore, the relationships between all prognostic factors and gene modules were explored, and the impact of these factors on treatment modalities was determined. RESULTS: We developed an efficient prognostic risk model and identified HOXA9, SORT1, SH3BP5, mir-224 and mir-335 as biomarkers. We validated these findings in an external dataset and observed a correlation between age and risk in pediatric patients. AML samples with lower risk scores have a better prognosis and higher expression of immune-upregulated biomarkers, and have lower immune scores. Furthermore, we detected discrepancies in immune cell infiltration and interactions between high- and low-risk group samples, which affected the efficacy of immunotherapy. We evaluated all prognostic factors and predicted the effect of immunotherapy and medicine. CONCLUSION: This study comprehensively investigated the role of methylation signature genes in pediatric AML at the level of genomes and transcriptomes. The research aims to enhance the risk stratification, prognosis evaluation and assessment of treatment effectiveness of AML patients. This study also highlight the uniqueness of pediatric AML and foster the development of new immunotherapy and targeted therapy strategies.

Embedding Nano-Piezoelectrics into Heterointerfaces of S-Scheme Heterojunctions for Boosting Photocatalysis and Piezophotocatalysis.

Step-scheme (S-scheme) heterojunctions have exhibited great potential in photocatalysis due to their extraordinary light harvesting and high redox capacities. However, inadequate S-scheme recombination of useless carriers in weak redox abilities increases the probability of their recombination with useful ones in strong redox capabilities. Herein, a versatile protocol is demonstrated to overcome this impediment based on the insertion of nano-piezoelectrics into the heterointerfaces of S-scheme heterojunctions. Under light excitation, the piezoelectric inserter promotes interfacial charge transfer and produces additional photocarriers to recombine with useless electrons and holes, ensuring a more thorough separation of powerful ones for CO2 reduction and H2 O oxidation. When introducing extra ultrasonic vibration, a piezoelectric polarization field is established, which allows efficient separation of charges generated by the embedded piezoelectrics and expedites their recombination with weak carriers, further increasing the number of strong ones participating in the redox reactions. Encouraged by the greatly improved charge utilization, significantly enhanced photocatalytic and piezophotocatalytic activities in CH4 , CO, and O2 production are achieved by the designed stacked catalyst. This work highlights the importance in strengthening the necessary charge recombination in S-scheme heterojunctions and presents an efficient and novel strategy to synergize photocatalysis and piezocatalysis for renewable fuels and value-added chemicals production.

Plasmonic Metal Mediated Charge Transfer in Stacked Core-Shell Semiconductor Heterojunction for Significantly Enhanced CO2 Photoreduction.

Construction of core-shell semiconductor heterojunctions and plasmonic metal/semiconductor heterostructures represents two promising routes to improved light harvesting and promoted charge separation, but their photocatalytic activities are respectively limited by sluggish consumption of charge carriers confined in the cores, and contradictory migration directions of plasmon-induced hot electrons and semiconductor-generated electrons. Herein, a semiconductor/metal/semiconductor stacked core-shell design is demonstrated to overcome these limitations and significantly boost the photoactivity in CO2  reduction. In this smart design, sandwiched Au serves as a "stone", which "kills two birds" by inducing localized surface plasmon resonance for hot electron generation and mediating unidirectional transmission of conduction band electrons and hot electrons from TiO2  core to MoS2  shell. Meanwhile, upward band bending of TiO2  drives core-to-shell migration of holes through TiO2 -MoS2  interface. The co-existence of TiO2  â†’ Au â†’ MoS2  electron flow and TiO2  â†’ MoS2  hole flow contributes to spatial charge separation on different locations of MoS2  outer layer for overall redox reactions. Additionally, reduction potential of photoelectrons participating in the CO2  reduction is elaborately adjusted by tuning the thickness of MoS2  shell, and thus the product selectivity is delicately regulated. This work provides fresh hints for rationally controlling the charge transfer pathways toward high-efficiency CO2  photoreduction.

DNA ploidy and stroma predicted the risk of recurrence in low-risk stage III colorectal cancer.

BACKGROUND: For clinically low-risk stage III colorectal cancer, the decision on cycles of adjuvant chemotherapy after surgery is disputed. The present study investigates the use of additional biomarkers of ploidy and stroma-ratio(PS) to stratify patients with low-risk stage III colorectal cancer, providing a basis for individualized treatment in the future. METHODS: This study retrospectively enrolled 198 patients with clinical-low-risk stage III colorectal cancer (T1-3N1M0) and analyzed the DNA ploidy and stroma ratio of FFPE tumor tissues. The patients were divided into PS-low-risk group (Diploidy or Low-stroma) and PS-high-risk group (Non-diploid and High-stroma). For survival analyses, Kaplan-Meier and Cox regression models were used. RESULTS: The results showed that the 5-year DFS of the PS-high-risk group was significantly lower than that in the PS-low-risk group (78.6 vs. 91.2%, HR = 2.606 [95% CI: 1.011-6.717], P = 0.039). Besides, in the PS-low-risk group, the 5 year OS (98.2 vs. 86.7%, P = 0.022; HR = 5.762 [95% CI: 1.281-25.920]) and DFS (95.6, vs 79.9%, P = 0.019; HR = 3.7 [95% CI: 1.24-11.04]) of patients received adjuvant chemotherapy for > 3 months were significantly higher than those received adjuvant chemotherapy for < 3 months. We also found that the PS could stratify the prognosis of patients with dMMR tumors. The 5-year OS (96.3 vs 71.4%, P = 0.037) and DFS (92.6 vs 57.1%, P = 0.015) were higher in the PS-low-risk dMMR patients than those in the PS-high-risk dMMR patients. CONCLUSION: In this study, we found that PS can predict the prognosis of patients with stage III low-risk CRC. Besides, it may guide the decision on postoperative adjuvant chemotherapy.

Comparison and Verification of Three Algorithms for Accuracy Improvement of Quartz Resonant Pressure Sensors.

Pressure measurement is of great importance due to its wide range of applications in many fields. AT-cut quartz, with its exceptional precision and durability, stands out as an excellent pressure transducer due to its superior accuracy and stable performance over time. However, its intrinsic temperature dependence significantly hinders its potential application in varying temperature environments. Herein, three different learning algorithms (i.e., multivariate polynomial regression, multilayer perceptron networks, and support vector regression) are elaborated in detail and applied to establish the prediction models for compensating the temperature effect of the resonant pressure sensor, respectively. The AC-cut quartz, which is sensitive to temperature variations, is paired with the AT-cut quartz, providing the essential temperature information. The output frequencies derived from the AT-cut and AC-cut quartzes are selected as input data for these learning algorithms. Through experimental validation, all three methods are effective, and a remarkable improvement in accuracy can be achieved. Among the three methods, the MPR model has exceptionally high accuracy in predicting pressure. The calculated residual error over the temperature range of -10-40 °C is less than 0.008% of 40 MPa full scale (FS). An intelligent automatic compensation and real-time processing system for the resonant pressure sensor is developed as well, which may contribute to improving the efficiency in online calibration and large-scale industrialization. This paper paves a promising way for the temperature compensation of resonant pressure sensors.

A Hardware System for Synchronous Processing of Multiple Marine Dynamics MEMS Sensors.

Temperature, depth, conductivity, and turbulence are fundamental parameters of marine dynamics in the field of ocean science. These closely correlated parameters require time-synchronized observations to provide feedback on marine environmental problems, which requires using sensors with synchronized power supply, multi-path data solving, recording, and storage performances. To address this challenge, this work proposes a hardware system capable of synchronously processing temperature, depth, conductivity, and turbulence data on marine dynamics collected by sensors. The proposed system uses constant voltage sources to excite temperature and turbulence sensors, a constant current source to drive a depth sensor, and an alternating current (AC) constant voltage source to drive a conductivity sensor. In addition, the proposed system uses a high-precision analog-digital converter to acquire the direct current (DC) signals from temperature, depth, and turbulence sensors, as well as the AC signals from conductivity sensors. Since the sampling frequency of turbulence sensors is different from that of the other sensors, the proposed system stores the generated data at different storage rates as multiple-files. Further, the proposed hardware system manages these files through a file system (file allocation tab) to reduce the data parsing difficulty. The proposed sensing and hardware logic system is verified and compared with the standard conductivity-temperature-depth measurement system in the National Center of Ocean Standards and Metrology. The results indicate that the proposed system achieved National Verification Level II Standard. In addition, the proposed system has a temperature indication error smaller than 0.02 °C, a conductivity error less than 0.073 mS/cm, and a pressure error lower than 0.8‱ FS. The turbulence sensor shows good response and consistency. Therefore, for observation methods based on a single point, single line, and single profile, it is necessary to study multi-parameter data synchronous acquisition and processing in the time and spatial domains to collect fundamental physical quantities of temperature, salt, depth, and turbulence. The four basic physical parameters collected by the proposed system are beneficial to the in-depth research on physical ocean motion, heat transfer, energy transfer, mass transfer, and heat-energy-mass coupling and can help to realize accurate simulation, inversion, and prediction of ocean phenomena.

Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer.

Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment. In silico investigation prompted by this observation confirms correlation between inflammatory conditions and poor tumor response to PD-1 blockade in MSI-H CRCs, which is further validated in a cohort of 62 patients retrospectively enrolled to our study. Inhibition of local but not systemic immune response is verified in cultures of paired T cells and organoid cells from patients. Single-cell RNA sequencing suggests involvement of neutrophil leukocytes via CD80/CD86-CTLA4 signaling in the suppressive immune microenvironment. In concordance with this finding, elevated neutrophil-to-lymphocyte ratio indicates inhibited immune status and poor tumor response to ICIs. Receiver operating characteristic curve further demonstrates that both inflammatory conditions and a high NLR could predict a poor response to ICIs in MSI- CRCs, and the predictive value could be further increased when these two predictors are combined. Our study thus suggests that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil leukocyte associated immunosuppression and proposes both inflammatory conditions and high neutrophil-to-lymphocyte ratio as clinical features for poor ICI response.

The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator.

Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan-Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46-0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04-2.05], p = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02-2.04], p = 0.038) were associated with worse RFS. Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.

Design, Fabrication, and Dynamic Environmental Test of a Piezoresistive Pressure Sensor.

Microelectromechanical system (MEMS) pressure sensors have a wide range of applications based on the advantages of mature technology and easy integration. Among them, piezoresistive sensors have attracted great attention with the advantage of simple back-end processing circuits. However, less research has been reported on the performance of piezoresistive pressure sensors in dynamic environments, especially considering the vibrations and shocks frequently encountered during the application of the sensors. To address these issues, this paper proposes a design method for a MEMS piezoresistive pressure sensor, and the fabricated sensor is evaluated in a series of systematic dynamic environmental adaptability tests. After testing, the output sensitivity of the sensor chip was 9.21 mV∙bar-1, while the nonlinearity was 0.069% FSS. The sensor overreacts to rapidly changing pressure environments and can withstand acceleration shocks of up to 20× g. In addition, the sensor is capable of providing normal output over the vibration frequency range of 0-5000 Hz with a temperature coefficient sensitivity of -0.30% FSS °C-1 over the temperature range of 0-80 °C. Our proposed sensor can play a key role in applications with wide pressure ranges, high-frequency vibrations, and high acceleration shocks, as well as guide MEMS-based pressure sensors in high pressure ranges and complex environmental adaptability in their design.

Chinese Consumers' Trust in Food Safety Surveillance Sampling of Commonly Consumed Foods.

In China, food has become safer over the past five years, especially commonly consumed foods. Food supervision sampling has played an important role in improving food safety. However, consumer acceptance of the results of food safety supervision have not kept pace. Communicating actual food safety risks to consumers and improving the public trust in food safety supervision sampling inspection has become an important issue. This study focused on food safety surveillance sampling of commonly consumed foods. In total, 4408 adult consumers were surveyed between August and October 2021. Structural equation modeling was performed for data analysis. This study found significant differences along gender lines and across different cities and levels of education with respect to evaluating competence trust and care trust on food supervision sampling inspection. This study identified the public's competence trust, care trust, and perception of food safety as factors that significantly affect one's attitude toward supervision sampling inspection. Care trust showed a more pronounced effect on trust enhancement than competence trust. The present study also provides some practical measures for food safety supervisors to improve public trust in the national food inspection. Specifically, the sampling process should be open and transparent.

[Effectiveness of penis up transfer method for penoscrotal transposition in children].

Objective: To investigate the effectiveness of penile up transfer method in the treatment of penoscrotal transposition (PST) in children. Methods: A clinical data of 46 children with PST admitted between January 2015 and March 2021 and met selective criteria was retrospectively analyzed. The M-shaped scrotal flap method was adopted in 21 cases (group A), and the penile up transfer method was adopted in 25 cases (group B). There was no significant difference in age and PST typing between the two groups ( t=0.491, P=0.626; χ 2=0.710, P=0.790). The operation time and postoperative complications of the two groups were recorded and compared, and the correction effect of PST was evaluated. Results: All operations were successfully completed, and no urethral injury occurred during operation. The operation time was significantly less in group B than in group A [(70.36±9.76) minutes vs. (96.62±13.18) minutes; t=7.553, P=0.000]. All children were followed up 6-33 months (mean, 13.2 months). There were 5 cases (23.8%) of skin necrosis and 6 cases (28.6%) of scar hyperplasia in group A, and 1 case (4.0%) of skin necrosis and 1 case (4.0%) of scar hyperplasia in group B. The incidence of complication was significantly lower in group B than in group A ( χ 2=3.949, P=0.047; χ 2=5.341, P=0.021). In the evaluation of PST correction at 6 months after operation, there were 15 cases of complete correction and 6 cases of incomplete correction in group A, 24 cases of complete correction and 1 case of incomplete correction in group B, and the difference was significant ( χ 2=5.341, P=0.021). Conclusion: The penis up transfer method is not only easy to correct PST, but also can correct scrotal separation at the same time, with fewer postoperative complications and satisfactory correction effect of penile scrotal appearance.

A novel score system for predicting conversion to no evidence of Disease (C-NED) in initially unresectable colorectal cancer liver metastases.

An estimated 70-80% of cases of colorectal cancer liver metastasis (CRLM) are defined as initially unresectable. "Converting" to no evidence of disease (NED) status may prolong survival. The current study aimed to develop a novel scoring system that predicts the conversion outcome for initially unresectable CRLM. A total of 215 consecutive CRLM patients who received first-line systemic therapy from December 2012 to January 2020 at Sun Yat-sen University Cancer Center were enrolled in the internal cohort. Forty CRLM patients from the database of the Chinese Colorectal Cancer Multidisciplinary Team Alliance were enrolled in the external cohort. A logistic regression model was applied to identify risk factors associated with the conversion outcome. The tumor-to-liver volume ratio (TLVR) was calculated as the total tumor volume divided by the total liver volume, and its cutoff value was 0.23. Three predictors of conversion failure were identified in the internal cohort and incorporated into the C-NED score: poor tumor differentiation (1 point), number of liver metastases > 8 (1 point) and TLVR ≥ 0.23 (1 point). The conversion rate was significantly negatively associated with the C-NED score (P < 0.001). The C-indexes of the C-NED score for predicting successful conversion outcome in the internal cohort and external cohort were 0.734 (95% confidence interval (CI), 0.668-0.800) and 0.736 (95% CIs, 0.566-0.907), respectively. Median progression-free survival (PFS) time (P = 0.001) and overall survival (OS) time (P = 0.003) were statistically significant different among different C-NED score groups. Our study demonstrated that the C-NED score is an effective scoring system that indicates the actual conversion probability for initially unresectable CRLM patients before treatment, which can serve as a tool that guides optimal first-line management strategies.

OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis.

BACKGROUND: Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. PATIENTS AND METHODS: Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. RESULTS: OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3ß, we verified GSK3ß was over-activated in OLA1-KO cell lines. CONCLUSION: OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3ß.

Emerging Stacked Photocatalyst Design Enables Spatially Separated Ni(OH)2 Redox Cocatalysts for Overall CO2 Reduction and H2 O Oxidation.

Construction of photocatalytic systems with spatially separated dual cocatalysts is considered as a promising route to modulate charge separation/transfer, promote surface redox reactivities, and prevent unwanted reverse reactions. However, past efforts on the loading of spatially separated double-cocatalysts are limited to hollow structured semiconductors with inner/outer surface and monocrystalline semiconductors with different exposed facets. To overcome this limitation, herein, enabled by a unique stacked photocatalyst design, a facile and versatile strategy for spatial separation of redox cocatalysts on various semiconductors without structural and morphological restriction is demonstrated. The smart design begins with the deposition of light-harvesting semiconductors on reduced graphene oxide (rGO) nanosheets, followed with the coverage of Ni(OH)2 outer layer. The ternary photocatalysts exhibit superior activities and stabilities of H2 O oxidation and selective CO2 -to-CO reduction, remarkably surpassing other counterparts. The origin of the enhanced performance is attributed to the synergistic interplay of rGO@Ni(OH)2 reduction cocatalysts surrounding the semiconductors and Ni(OH)2 oxidation cocatalysts directly supported by the semiconductors, which mitigates the charge recombination, supplies highly active and selective sites for overall reactions, and preserves the semiconductors from photocorrosion. This work presents a new approach to regulating the position of dual cocatalysts and ameliorating the net efficiency of photoredox catalysis.