Flexible and Compressible Nanostructure-Assembled Aramid Nanofiber/Silica Composites Aerogel.

The Applications of silica aerogel are limited due to its brittleness and low strength. As a result, it is essential to strengthen and toughen it. Organic nanofibers are one of the preferred reinforcement materials. In this work, we designed and fabricated flexible and compressible nanostructure-assembled aramid nanofiber/silica composites aerogel (ANF/SiO2 aerogel) to improve the mechanical strength and flexibility of silica aerogel without compromising thermal insulation properties. The aramid nanofiber/silica composite aerogels were prepared by immersing the aramid nanofiber wet gel into the silica sol for a certain period of time followed by freeze drying without solvent replacement. The surface modifier 3-aminopropyltriethoxysilane (APTES) was used as a coupling agent to form chemical linkage between the ANF fiber and silica gel. It was observed that APTES can effectively drive the silica sol to infuse into ANF hydrogel, promoting the assembly of silica gel onto the fiber surface and a uniform distribution in the network of ANF. The compressive resilience, thermal stability, and thermal insulation properties of the composite aerogels were evaluated by inducing the silica aerogel into the ANF network to form a protective layer on the fiber and change the pore structure in the ANF network.

Research on the Shale Reservoir Sensitivity by Using the Mineral Analysis Method.

Shale reservoirs have diverse mineral types, and analyzing the sensitivity of the mineral composition to shale pores is of great scientific and engineering significance. In this paper, first, X-ray diffraction (XRD) experiments on shale mineral compositions are carried out, and the characteristics of pore structure changes after shale mineral compositions interacted with external fluids (slick water and backflow fluid) are elucidated. Then, the effects of quartz, kaolinite, and pyrite on the pore structure and permeability of shale on the susceptibility to slick water are studied. The results show that (a) quartz and clay minerals are the dominant constituents of each core, with some cores containing minor amounts of plagioclase feldspar and rhodochrosite. (b) The composition of the shale changed significantly following the action of external fluids. The average quartz content of pure shale decreased from 31.62% to 29.1%. The average content of quartz in siliceous shale decreased from 36.53% to 33.5%. The average content of quartz in carbonaceous shale decreased from 9.15% to 8.05%. (c) Factors affecting the sensitivity of shale pore structure and permeability to slick water are mainly quartz, kaolinite, and pyrite. The contents of quartz, kaolinite, and pyrite decreased by an average of 5.1%, 4.6%, and 0.9%, respectively, after slick water action.

Biological impact and therapeutic potential of a novel camptothecin derivative (FLQY2) in pancreatic cancer through inactivation of the PDK1/AKT/mTOR pathway.

BACKGROUND: Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity. Despite extensive development efforts, many of these derivatives have not succeeded clinically, particularly in their effectiveness against pancreatic cancer which remains modest. AIM OF THE STUDY: This study aimed to evaluate the therapeutic activity of FLQY2, a CPT derivative synthesized in our laboratory, against pancreatic cancer, comparing its efficacy and mechanism of action with those of established clinical drugs. METHODS: The cytotoxic effects of FLQY2 on cancer cells were assessed using an MTT assay. Patient-derived organoid (PDO) models were employed to compare the sensitivity of FLQY2 to existing clinical drugs across various cancers. The impact of FLQY2 on apoptosis and cell cycle arrest in Mia Paca-2 pancreatic cancer cells was examined through flow cytometry. Transcriptomic and proteomic analyses were conducted to explore the underlying mechanisms of FLQY2's antitumor activity. Western blotting was used to determine the levels of proteins regulated by FLQY2. Additionally, the antitumor efficacy of FLQY2 in vivo was evaluated in a pancreatic cancer xenograft model. RESULTS: FLQY2 demonstrated (1) potent cytotoxicity; (2) superior tumor-suppressive activity in PDO models compared to current clinical drugs such as gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infinitinib, and lenvatinib; (3) significantly greater tumor inhibition than paclitaxel liposomes in a pancreatic cancer xenograft model; (4) robust antitumor effects, closely associated with the inhibition of the TOP I and PDK1/AKT/mTOR signaling pathways. In vitro studies revealed that FLQY2 inhibited cell proliferation, colony formation, induced apoptosis, and caused cell cycle arrest at nanomolar concentrations. Furthermore, the combination of FLQY2 and gemcitabine exhibited significant inhibitory and synergistic effects. CONCLUSION: The study confirmed the involvement of topoisomerase I and the PDK1/AKT/mTOR pathways in mediating the antitumor activity of FLQY2 in treating Mia Paca-2 pancreatic cancer. Therefore, FLQY2 has potential as a novel therapeutic option for patients with pancreatic cancer.

Comparative Epigenetic Profiling Reveals Distinct Features of Mucosal Melanomas Associated with Immune Cell Infiltration and Their Clinical Implications.

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomical sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 mucosal melanoma patients, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared to NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of PMME patients and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.

Clinically Applicable Pan-Origin Cancer Detection for Lymph Nodes via AI-Based Pathology.

Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent. Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole slide images and is composed of two deep learning models to locate the lymph nodes and detect cancers. It achieved a area under the receiver operating characteristic (ROC) curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 whole-slide images (WSIs) from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical center, with a AUC of 0.925. Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.

The Effectiveness and Optimal Timing of PEG-rhG-CSF After Autologous Peripheral Blood Stem Cell Transplantation: A Multicenter Experience.

No consensus has been made on the use of PEG-modification recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in patients receiving autologous peripheral blood stem cell transplantation (PBSCT). To evaluate the efficacy and safety of PEG-rhG-CSF in provision of neutrophil support for lymphoma patients receiving autologous PBSCT. This retrospective study included lymphoma patients receiving either PEG-rhG-CSF or rhG-CSF after autologous PBSCT from 2018 to 2021 in two clinics. Hematologic recovery time, incidence of infectious complications and toxicity were compared between these two rhG-CSFs and among different initiation time of PEG-rhG-CSF. Of the 139 subjects included, 93 received PEG-rhG-CSF and 46 received rhG-CSF after transplantation. Compared with rhG-CSF, PEG-rhG-CSF marginally but significantly accelerated the neutrophil engraftment by 1 day (10 vs. 9 days, respectively) with no increasing on the risk of infectious complication and toxicity. In the PEG-rhG-CSF group, 50 patients received the growth factor on day 1, 19 received on day 3 and 24 received on day 5. The neutrophil engraftment was significantly shorter in day 1 and day 3 subgroup (9, 9, and 10 days, respectively), with a lower incidence of febrile neutropenia (82%, 100%, 100%) and documented infections (76%, 100%, 100%) in day 1 subgroup. PEG-rhG-CSF might be an alternative to rhG-CSF for lymphoma patients received autologous PBSCT. Administrating PEG-rhG-CSF on day 1 can achieve both faster hematologic recovery and lower infectious complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01704-8.

Stereoselective and controllable C3-Amination or C1,C3-di-amination of 2-nitroglycals.

Precise and selective modification of carbohydrates is a critical strategy in producing diverse carbohydrate derivatives for exploiting their functions. We disclosed a simple, efficient, and highly regioselective and stereoselective protocol to controllable amination of 2-nitroglycals under mild conditions in 5 min. A range of 3-amino-carbohydrates including 3-arylamino-2-nitro-glycals and 1,3-di-amino-carbohydrate derivatives were obtained in good to excellent yield with excellent stereoselectivity. The produced 3-amino-2-nitro-glycals can be used as a precursor for further transformation.

Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) stands as one of the numerous debilitating consequences that follow traumatic brain injury (TBI). Despite its impact on many individuals, the current landscape offers only a limited array of reliable treatment options, and our understanding of the underlying mechanisms and susceptibility factors remains incomplete. Among the potential contributors to epileptogenesis, astrocytes, a type of glial cell, have garnered substantial attention as they are believed to promote hyperexcitability and the development of seizures in the brain following TBI. The current study evaluated the transcriptomic changes in cortical astrocytes derived from animals that developed seizures as a result of severe focal TBI. Using RNA-Seq and ingenuity pathway analysis (IPA), we unveil a distinct gene expression profile in astrocytes, including alterations in genes supporting inflammation, early response modifiers, and neuropeptide-amidating enzymes. The findings underscore the complex molecular dynamics in astrocytes during PTE development, offering insights into therapeutic targets and avenues for further exploration.

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. METHODS AND RESULTS: A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. CONCLUSIONS: Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Comprehensive analysis of m6A methylome alterations after azacytidine plus venetoclax treatment for acute myeloid leukemia by nanopore sequencing.

N6 adenosine methylation (m6A), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of m6A regulators on acute myeloid leukemia (AML). However, the global m6A levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear. In our present study, bone marrow (BM) sample pairs (including pre-treatment [AML] and post-treatment [complete remission (CR)] samples) were harvested from three AML patients who had achieved CR after AZA plus VEN treatment for Nanopore direct RNA sequencing. Notably, the amount of m6A sites and the m6A levels in CR BMs was significantly lower than those in the AML BMs. Such a significant reduction in the m6A levels was also detected in AZA-treated HL-60 cells. Thirteen genes with decreased m6A and expression levels were identified, among which three genes (HPRT1, SNRPC, and ANP32B) were closely related to the prognosis of AML. Finally, we speculated the mechanism via which m6A modifications affected the mRNA stability of these three genes. In conclusion, we illustrated for the first time the global landscape of m6A levels in AZA plus VEN treated AML (CR) patients and revealed that AZA had a significant demethylation effect at the RNA level in AML patients. In addition, we identified new biomarkers for AZA plus VEN-treated AML via Nanopore sequencing technology in RNA epigenetics.

Evolutionary Identification of the Requirement of the Second Intracellular Loop for the Constitutive Activity of Melanocortin-4 Receptors.

Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residues of F149, Q156, V163, and K164 of the second intracellular loop played a vital role in determining MC4R constitutive activity. This study provided novel insights into functional evolution and identified a key motif essential for constitutive modulation of MC4R signaling.

Research on the integrated solution of physical education based on smart campus.

To improve the physical education experience for students, this study investigates the idea of an integrated solution based on a smart campus for physical education. Within the physical education curriculum, the study focuses on the integration of smart fitness monitoring and wearables, interactive fitness equipment and gamification, mobile applications and customized workout plans, smart facilities, indoor navigation, and data-driven curriculum enhancements. The data gathered from a study involving two groups of students, an experimental group with access to smart campus solutions and a control group without such access, was analyzed using an organized and component-based framework. The data study looks at how the smart campus solutions affect the students' academic performance, fitness levels, motivation, and adherence to exercise regimens. The analyzed findings point to a few advantages of using smart campus technologies in physical education. Compared to the control group, students in the experimental group showed higher levels of academic performance, increased motivation, improved exercise adherence, and fitness. Students who had access to smart campus solutions reported much better experiences with physical education overall. The results imply that smart campus technologies have the potential to produce a physical education learning environment that is more interesting, focused on the needs of the students, and effective. Smart campus solutions help optimize curriculum design, boost motivation, and enhance academic performance by utilizing data-driven insights and personalized learning experiences.NEW & NOTEWORTHY This study investigates the idea of an integrated solution based on a smart campus for physical education. Within the physical education curriculum, the study focuses on the integration of smart fitness monitoring and wearables, interactive fitness equipment and gamification, mobile applications and customized workout plans, smart facilities, indoor navigation, and data-driven curriculum enhancements.

Nickel and Chiral Phosphoric Acid Cocatalysis Enables Synthesis of C-Acyl Glycosides.

We disclosed a Ni/CPA cocatalyzed protocol to access diverse C-acyl glycosides under mild conditions with broad functional group compatibility through the coupling of readily available glycosyl bromides and carboxylic esters. The potential application of the methodology was demonstrated by the C-acyl glycosylation of bioactive molecules and the transformation of products to a variety of value-added molecules. Mechanistic studies revealed that CPA might serve as a bifunctional H-bond catalyst to activate carboxylic esters and nickel catalyst.

Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA). METHODS: Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis. RESULTS: Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01). CONCLUSIONS: Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

Research and optimization of hydrogen addition and EGR on the combustion, performance, and emission of the biodiesel-hydrogen dual-fuel engine with different loads based on the RSM.

Pollutants produced by engines are a significant source of environmental pollution, so the study of engine emissions is very important. In this study, with CONVERGE software, a diesel engine model of the engine was produced. To better obtain the characteristic results of the engine, this was coupled with an improved chemical kinetics mechanism. Then, the results of this model were verified experimentally. Additionally, the effects of four different EGR rates on the combustion, performance, and emissions of a dual-fuel diesel engine were investigated by the verified model under different (50 %, 75 %, and 100 %) load conditions. Lastly, the brake specific fuel consumption, NOx emission, and HC emission were optimized by the response surface methodology (RSM). The results show that the pressure, temperature, and NOx emission in the engine's cylinder can all be reduced by raising the EGR at three different loads. Besides, the optimization results show that the engine achieves the best operating conditions at 100 % load, hydrogen fraction of 6.92 %, and EGR rate of 7.68 %.

Proficiency testing of diagnosis in histopathology and immunohistochemistry of breast pathology in China: results from a pilot work of National Single Disease Quality Control Program for breast cancer.

AIM: Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China. METHODS: This national PT plan is designed and implemented according to the "Conformity assessment-General requirements for proficiency testing" (GB/T27043-2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 ). RESULTS: Our study demonstrated that the median PT score was 89.5 (54-100). Two institutions with scores < 67 were deemed unacceptable. The accuracy of histologic type, ER, PR, HER2, and Ki67 was satisfactory (all > 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR < 1% weak expression as positive staining (1.4%), and no evaluation of histologic grade in ILC, MC, and IMC (5.8%). CONCLUSIONS: our nationwide PT program exhibited a satisfactory baseline assessment of the diagnostic capability of pathologists in China. More importantly, we identify some areas for further improvement.

Analysis of false reasons based on the artificial intelligence RRCART model to identify frozen sections of lymph nodes in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor in the world. Intraoperative frozen section of sentinel lymph nodes is an important basis for determining whether axillary lymph node dissection is required for breast cancer surgery. We propose an RRCART model based on a deep-learning network to identify metastases in 2362 frozen sections and count the wrongly identified sections and the associated reasons. The purpose is to summarize the factors that affect the accuracy of the artificial intelligence model and propose corresponding solutions. METHODS: We took the pathological diagnosis of senior pathologists as the gold standard and identified errors. The pathologists and artificial intelligence engineers jointly read the images and heatmaps to determine the locations of the identified errors on sections, and the pathologists found the reasons (false reasons) for the errors. Through NVivo 12 Plus, qualitative analysis of word frequency analysis and nodal analysis was performed on the error reasons, and the top-down error reason framework of "artificial intelligence RRCART model to identify frozen sections of breast cancer lymph nodes" was constructed based on the importance of false reasons. RESULTS: There were 101 incorrectly identified sections in 2362 slides, including 42 false negatives and 59 false positives. Through NVivo 12 Plus software, the error causes were node-coded, and finally, 2 parent nodes (high-frequency error, low-frequency error) and 5 child nodes (section quality, normal lymph node structure, secondary reaction of lymph nodes, micrometastasis, and special growth pattern of tumor) were obtained; among them, the error of highest frequency was that caused by normal lymph node structure, with a total of 45 cases (44.55%), followed by micrometastasis, which occurred in 30 cases (29.70%). CONCLUSIONS: The causes of identification errors in examination of sentinel lymph node frozen sections by artificial intelligence are, in descending order of influence, normal lymph node structure, micrometastases, section quality, special tumor growth patterns and secondary lymph node reactions. In this study, by constructing an artificial intelligence model to identify the error causes of frozen sections of lymph nodes in breast cancer and by analyzing the model in detail, we found that poor quality of slices was the preproblem of many identification errors, which can lead to other errors, such as unclear recognition of lymph node structure by computer. Therefore, we believe that the process of artificial intelligence pathological diagnosis should be optimized, and the quality control of the pathological sections included in the artificial intelligence reading should be carried out first to exclude the influence of poor section quality on the computer model. For cases of micrometastasis, we suggest that by differentiating slices into high- and low-confidence groups, low-confidence micrometastatic slices can be separated for manual identification. The normal lymph node structure can be improved by adding samples and training the model in a targeted manner.

Network Pharmacology and Molecular Modeling Techniques in Unraveling the Underlying Mechanism of Citri Reticulatae Pericarpium aganist Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a common complication in diabetic patients that seriously affects their health and quality of life. The pathogenesis of T2DOP is complex, and there are no targeted governance means in modern medicine. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese medicine that has a long history and has been used in the treatment of osteoporosis diseases. However, the molecular mechanism for the CRP treatment of T2DOP is not clear. Therefore, this study aimed to explore the underlying mechanisms of CRP for the treatment of T2DOP by using network pharmacology and molecular modeling techniques. By retrieving multiple databases, we obtained 5 bioactive compounds and 63 common targets of bioactive compounds with T2DOP, and identified AKT 1, TP 53, JUN, BCL 2, MAPK 1, NFKB 1, and ESR 1 as the core targets of their PPI network. Enrichment analysis revealed that these targets were mainly enriched in the estrogen signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetics, which were mainly related to oxidative stress and hormonal regulation. Molecular docking and molecular dynamics simulations have shown the excellent binding effect of the bioactive compounds of CRP and the core targets. These findings reveal that CRP may ameliorate T2DOP through multiple multicomponent and multitarget pathways.