With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To study the accuracy and safety of oral mucosal exfoliated cell specimens used in the bedside rapid detection of MTHFR C677T genotype by using the fluorescent probe method.Methods The outpatients and inpatients with hypertension visited and admitted in the department of cardiovascular medicine of this hospital from January 2019 to September 2020 were selected.The plasma homocysteine (Hcy) level in all patients was detected in the laboratory,a total of 482 hypertensive patients with Hcy≥10 μmol/L were se-lected,and the oral mucosal cells and whole blood sample were collected in all patients,and the genotypes of the above specimens were detected by the oral mucosal exfoliative cell fluorescent probe method and whole blood sample contrast reagents.If the two test results were inconsistent,the "gold standard" Sanger sequen-cing method was used to detect the whole blood sample for the final determination of MTHFR C677T geno-type.The coincidence rate was compared between the two detection methods,and the probability of adverse e-vents during the samples collection was observed and recorded.The accuracy and safety of fluorescence probe method for detecting MTHFR C677T genotype in the patients with oral mucosa exfoliation was evaluated.Re-sults The oral mucosal exfoliated cell samples and whole blood samples from 482 hypertensive patients were successfully collected,and no obvious adverse reactions occurred during the sampling process.The incidence rate of total mutation of MTHFR C677T gene detected by the fluorescence probe method and contrast reagent all were 73.23％ (353/482),the coincidence rate of homozygous wild type (CC type) in MTHFR C677T gene detected by the two methods was 100.00％ (95％CI:97.11-100.00),which of heterozygous mutant type (CT type) was 99.14％ (95％CI:96.91-99.76),which of homozygous mutant type (TT type) was 99.17％(95％CI:95.47-99.85),the total coincident rate of MTHFR C677T genotype was 99.38％ (95％CI:98.19-99.79)and the detection results consistency Kappa value was 0.9902.Conclusion The detection of MTHFR C677T gene mutation in oral mucosal exfoliated cells by fluorescent probe method is simple with less invasion,moreover which is rapid,safe and accurate.

Objective To prepare quercetin nanocrystals,improve their dissolution rate,and investigate the effects of different stabilizer types and ratios on the stability of nanocrystals.Methods Quercetin nanocrystals were prepared by solvent ultrasonication,and three different stabilizers(polyvinylpyrrolidone-K30,poloxamer F188 and sodium dodecyl sulfate)were compared.The particle size was used as a screening index to investigate the stability of placement,the microscopic morphology of nanocrystals was characterized by scanning electron microscopy,infrared spectroscopy and X-ray diffraction,and the mechanism of action between stabilizers and nanocrystals was discussed.Results Through experimental screening,the results showed that povidone K30 had the best stable performance,the nanocrystals were also in the form of rod crystals,and the dissolution rate of nanocrystals was significantly higher than that of active pharmaceutical ingredients.Conclusion The type and amount of stabilizer will affect the stability of nanocrystals.

Objective To investigate the mechanism of influence of different oxygen concentrations on the composting process of solid biomass waste to determine the optimal oxygen parameters for future controlled ecological life support system(CELSS)solid waste treatment on extraterrestrial planet bases and enhance oxygen utilization efficiency.Methods Using the self-developed solid waste bioreactor test system,aerobic composting experiments were conducted on wheat straw and simulated manure with three different oxygen concentrations of 10%,15%,and 21%.Gas components(O2,NH3,CH4,and N2O)and material maturity indicators(moisture content,dissolved organic carbon,NH4+-N,and seed germination index)were regularly analyzed throughout the treatment process.Results The 15%O2 treatment group had the highest oxygen consumption,the lowest emissions of NH3 and N2O,the best degradation effect of dissolved organic carbon content and the higher NH4+-N content.CH4 emissions in the three treatment groups were all at a low level.At the end of composting,the moisture content of the products in the 10%O2 and 15%O2 treatment groups was all higher than 74%,and the water-holding capacity was the best.The seed germination indexes in the 3 treatment group were 86.64%,123.81%,and 97.98%,respectively.Conclusion Com pared to oxygen concentrations of 10%and 21%,the 15%oxygen concentration can effectively reduce the emission of NH3 and N2O.It also improves nitrogen and water retention,enhances dissolved organic carbon degradation effects,and results in higher maturity levels.

During the process of dairy farming,various factors such as physical injury and bacterial infection act upon body tissues or organs,leading to the disruption of skin or mucous tissue integ-rity and subsequent tissue injury and trauma.The healing of these injuries is a complex process that necessitates the coordinated efforts of different cells and involvement of diverse cytokines.A-mong them,the interaction between macrophages and myofibroblasts is indispensable for efficient tissue repair.Nod-like receptor protein 3(NLRP3),a pattern recognition receptor in the innate im-mune system,may play a regulatory role in modulating this intricate process.In this study,cow myofibroblasts and M1 type bone marrow-derived macrophages were cultured in vitro,followed by collection of cell culture supernatant for co-culture analysis.Both cytokine secretion levels in M1 type bone marrow-derived macrophages as well as expression patterns levels of myofibroblast growth factor protein and mRNA were detected.The regulatory mechanism underlying NLRP3 in-volvement in mediating interactions between these two cell types was investigated using NLRP3 inhibitor MCC950.The results showed that an effective method for culturing cow muscle fibroblasts in vitro was successfully established and myofibroblast conditioned medium(MFbCM)could regulate M1 macrophage secretion profiles.Moreover,M1 macrophage conditioned medium(M1?CM)was found to influence myofibroblast growth factor expression levels.Our findings sug-gest that NLRP3 plays a significant regulatory role during crosstalk between myofibroblasts and M1-type pro-inflammatory macrophages.

Objective:To analyze clinical features, short-term efficacy and side effects of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy, to investigate the prognostic factors of re-irradiation with precise radiotherapy techniques.Methods:A retrospective analysis was performed on patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy treated in the Fourth Hospital of Hebei Medical University from January 2008 to December 2016. The patients underwent re-irradiation therapy (re-RT) or re-irradiation therapy concurrent chemotherapy (re-CCRT). The main observation index was after-recurrence survival (ARS), which was calculated by Kaplan-Meier method for survival analysis. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox regression model.Results:A total of 109 patients were included, with a median age of 66 years (43-89 years), and a median follow-up time of 120.8 months (79.0-176.5 months). The objective response rates (ORR) and dysphagia improvement rates (DIR) in all patients were 64.2% and 63.0%, respectively. The median ARS and 1-, 3-, 5-, 8-year survival rates in all patients were 7.8 months and 32.1%, 9.2%, 7.3% and 2.3%, respectively. The median ARS and 1-, 3-, 5-years survival rates were 10.8 months and 45.9%, 13.5%, 10.8% for patients with time to recurrence (TTR) ≥24 months, significantly longer than those of 5.7 months and 25.0%, 6.9%, 5.6% for patients with TTR<24 months ( χ2=7.99, P=0.005). The median ARS in groups with re-irradiation dose of ≤50 Gy,>50-54 Gy, and>54 Gy groups were 5.7, 10.0 and 8.1 months, respectively ( χ2=6.94, P=0.031). The 1-, 3- and 5-year survival rates were 30.4%, 5.1%, and 3.8% for re-RT versus 36.7%, 20.0%, and 16.7% for re-CCRT ( χ2=2.12, P=0.145). Multivariate analysis showed that TTR ( HR=0.607, 95% CI=0.372-0.991, P=0.046) and lesion length ( HR=0.603, 95% CI=0.371-0.982, P=0.042) were the independent factors for ARS. There was no significant difference in ≥2 grade pneumonitis and 2-3 grade radiation esophagitis between the re-RT and re-CCRT groups ( χ2=0.25, P=0.619; χ2=0.51, P=0.808). The morbidity of ≥2 grade myelosuppression in the re-RT group was significantly lower than that in the re-CCRT group (3.7% vs. 36.7%, χ2=18.15, P<0.001). Conclusions:Precise re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy can alleviate dysphagia, but ARS remains poor. Re-irradiation dose range from>50-54 Gy may be suitable for locally relapse patients as salvage treatment. Patients with TTR≥24 months and lesion length ≤5 cm obtain favorable prognosis.

Objective:To learn about the implementation of prevention and control measures in drinking water-borne endemic fluorosis areas and the trend of the disease change in Jiangsu Province.Methods:In March to October 2021, a general survey was carried out in 1 972 villages with drinking water-borne endemic fluorosis in 27 counties (cities and districts) of Jiangsu Province, the operation of water improvement projects in the villages was monitored, and the water fluoride content was determined. The prevalence of dental fluorosis among children aged 8 to 12 years in all the villages was investigated.Results:The 1 972 villages with drinking water-borne endemic fluorosis had completed water improvement, and all water improvement projects were operating normally and the water was qualified. Among them, 1 774 villages in the disease affected areas had achieved the control goal, accounting for 89.96%; and there were 198 villages in the disease affected areas with control measures up to the standard, accounting for 10.04%. A total of 47 water improvement projects were monitored, including 2 small-scale water improvement projects, accounting for 4.26%. There were 45 large-scale water improvement projects, accounting for 95.74%. A total of 125 790 children aged 8 to 12 years were examined, and 12 625 cases of dental fluorosis were detected. The detection rate of dental fluorosis was 10.04%, and the dental fluorosis index was 0.19. The detection rate of dental fluorosis in children aged 8 to 12 years was 9.98% (1 854/18 579), 10.27% (2 704/26 323), 9.48% (2 765/29 152), 9.73% (2 835/29 145) and 10.92% (2 467/22 591), respectively, with statistically significant difference (χ 2 = 10.51, P = 0.015). Among the 198 villages with control measures up to standard, according to the historical water fluoride, the detection rate of dental fluorosis in children in each water fluoride range (1.20-2.00, 2.01-3.00, 3.01-4.00, > 4.00 mg/L) was 37.73% (698/1 850), 43.17% (1 176/2 724), 45.50% (769/1 690) and 55.20% (802/1 453), respectively, with a statistically significant difference (χ 2 = 104.15, P < 0.001). Conclusion:The water improvement measures in drinking water-borne endemic fluorosis areas in Jiangsu Province have achieved significant results, which still need to be further consolidated.

Objective:To dynamically observe the changes in iodine level in residents' drinking water after the change of regional water supply mode (2020) in Jiangsu Province.Methods:The survey of water iodine level was conducted from June to October 2020 in administrative villages of Jiangsu Province with a median water iodine ≥40 μg/L in 2017. The survey mainly covered 1 537 administrative villages in 21 counties (cities and districts) of 5 cities, including Huaian City, Lianyungang City, Suqian City, Yancheng City, and Xuzhou City. Based on the standard of "Definition and Demarcation of Iodine Deficient Areas and Iodine Adequate Areas" (WS/T 669-2020), the administrative villages with a median water iodine of 40 - 100 μg/L were classified as iodine adequate areas. Water iodine testing was conducted using the "Method for Water Iodine Testing in Iodine Deficient and High Iodine Areas" recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:Totally 1 498 administrative villages in Jiangsu Province were monitored in 2020, all of which had centralized water supply. The minimum value of water iodine in all administrative villages was 1.2 μg/L and the maximum value was 606.7 μg/L, and the median water iodine was 35.2 μg/L. Among them, 206 administrative villages had median water iodine < 10 μg/L, accounting for 13.75% (206/1 498); 610 administrative villages had median water iodine from 10 to < 40 μg/L, accounting for 40.72% (610/1 498); 635 administrative villages had median water iodine from 40 to 100 μg/L, accounting for 42.39% (635/1 498); and 47 administrative villages with median water iodine > 100 μg/L, accounting for 3.14% (47/1 498). Except for Sucheng District in Suqian City, Xinyi City and Gulou District in Xuzhou City, Qingjiangpu District and Xuyi County in Huaian City, and Guannan County in Lianyungang City, the median water iodine in the administrative villages of the remaining 15 counties (cities and districts) in 2020 decreased significantly compared to 2017, and the differences were statistically significant ( P < 0.05). Conclusion:After change of regional water supply mode in 2020, in most monitored counties (cities and districts) of Jiangsu Province, the water iodine level of administrative villages has decreased significantly compared to 2017.

Polyethylene terephthalate (PET) is one of the most widely used synthetic polyester. It poses serious threat to terrestrial, aquatic ecosystems and human health since it is difficult to be broken down and deposited in the environment. The biodegradation based on enzymatic catalysis offers a sustainable method for recycling PET. A number of PET hydrolases have been discovered in the last 20 years, and protein engineering has increased their degradation capabilities. However, no PET hydrolases that are practical for widespread industrial use have been identified. Screening of PET hydrolase using conventional detection techniques is laborious and inefficient process. Effective detection techniques are required to promote the commercialization of PET hydrolases. Using efficient detection techniques to screen potent industrial enzymes is essential for supporting the widespread industrial implementation of PET hydrolases. To define PET hydrolase, scientists have created a number of analytical techniques recently. The detection techniques that can be used to screen PET hydrolase, including high performance liquid chromatography, ultraviolet absorption spectrometric, and fluorescence activated droplet sorting method, are summarized in this study along with their potential applications.
Humans ; Polyethylene Terephthalates ; Ecosystem ; Biodegradation, Environmental ; Catalysis ; Hydrolases