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 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 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 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 analyze the iodine nutrition status of key populations in water source high iodine areas in Jiangsu Province, providing a reference for scientific prevention and control of water source high iodine hazards.Methods:From May to June 2020, monitoring sites were determined by administrative villages in six high iodine counties (cities, districts) in Jiangsu Province, and drinking water samples were collected from residents to detect the iodine content in the water; 40 non boarding children aged 8 - 10 from one primary school in each village (half male and half female, with an age balance) and 20 pregnant women were selected. Salt samples were taken from children and pregnant women's homes, and urine samples were randomly taken once to detect salt and urine iodine contents. Thyroid volume of children was examined.Results:A total of 36 administrative villages were monitored, with a median of 45.3 μg/L for water iodine, ranging from 8.5 - 372.1 μg/L. A total of 1 422 salt samples were collected, of which 26 were iodized salt, accounting for 1.83%; and 1 396 non iodized salt, with the coverage rate of non iodized salt was 98.17%. A total of 1 365 urine samples were collected from children, with a median urine iodine of 405.6 μg/L. There were statistically significant differences in urine iodine levels among children in different regions, drinking water iodine contents, and age groups ( H = 128.39, 67.81, 39.94, P < 0.001). A total of 57 urine samples were collected from pregnant women, with a median urine iodine of 282.0 μg/L. There were statistically significant differences in urine iodine levels among pregnant women in different regions and drinking water iodine contents groups ( H = 17.54, 18.39, P < 0.001). A total of 1 365 children's thyroid volumes were examined, and 44 cases of thyroid enlargement were detected, with a goiter rate of 3.22%. There were no statistically significant differences in the incidence of thyroid enlargement among children in different regions, drinking water iodine contents, salt types, gender, and age groups ( P > 0.05). Conclusions:The iodine nutrition of children in water source high iodine areas in Jiangsu Province is at an iodine excess level, while the iodine nutrition of pregnant women is at an over optimal level. In areas with high iodine content in water sources, the iodine content in drinking water has a significant impact on the iodine intake of the local population. There is currently no correlation between the iodine content in drinking water, salt type, gender, and age factors and thyroid enlargement in children.

Objective:To explore the feasibility of contrast-enhanced ultrasound in assessing the degree of transplant renal artery stenosis(TRAS)and evaluate its diagnostic efficacy of severe TRAS.Methods:From February 2013 to February 2022, clinical and follow-up data are retrospectively reviewed for 23 TRAS recipients.A definite diagnosis is made by magnetic resonance angiography (MRA, 2 cases)or digital subtraction angiography(DSA, 21 cases). They are assigned into two groups of mild-moderate stenosis(5 cases)and severe stenosis(18 cases)according to the diameter reduction rate of transplanted renal artery detected by DSA/MRA.Another 32 recipients of stable renal function are selected as controls.All contrast-enhanced ultrasonic images are quantitatively processed with SonoLiver.The following quantitative parameters are obtained, including rising time of interlobular artery(RTi), rising time of cortex(RTc), rising time of medulla(RTm), time to peak of interlobular artery(TTPi), time to peak of cortex(TTPc)and time to peak of medulla(TTPm). The differences of contrast-enhanced ultrasonic quantitative parameters are compared among three groups.And their diagnostic efficacies are calculated in the diagnosis of severe TRAS.Results:As compared with those in normal group, RTi, RTc, TTPi and TTPc are significantly longer in mild-moderate stenosis group(all P<0.05); Meanwhile, RTi, RTc, RTm, TTPi, TTPc and TTPm are significantly longer in severe stenosis group than those in normal group(all P<0.05); Comparing mild-moderate stenosis and severe stenosis groups, only RTm is significantly different between two groups( P<0.05). Among all the above parameters, RTc has the highest diagnostic efficacy in the diagnosis of severe TRAS(AUC=0.848)with a sensitivity of 72.22%, a specificity of 86.49% and an accuracy of 81.82%. Conclusions:The quantitative parameters of contrast-enhanced ultrasound offer aid in assessing the degree of TRAS.And RTc is the most valuable in the diagnosis of severe TRAS.

ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis （UC） mice induced by dextran sodium sulfate （DSS） and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group and and low-， medium-， and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group， other groups were given 1.5% DSS for 3 cycles of drinking （days 1-7， days 22-28 and days 43-49） and distilled water for the rest of the time （days 8-21， days 29-42 and days 50-63）. After the first cycle， corresponding drugs were given for 42 days. The changes of general condition， body weight and disease activity index （DAI） score of mice were daily recorded during the experiment. At the end of the treatment， serum and colon tissue samples were collected， colon length was measured， intestinal weight index and colonic mucosal injury （CMDI） score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin （HE） staining. The levels of interleukin-6 （IL-6）， interleukin-10 （IL-10） and tumour necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The gene and protein expressions of Toll like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB） and hypoxia inducible factor-1α （HIF-1α） in colon tissue was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the body weight， colon length and IL-10 content in the model group were significantly decreased （P<0.01）， DAI score， intestinal weight index， CMDI score， IL-6 and TNF-α contents， and mRNA and protein expression levels of TLR4， NF-κB and HIF-1α in the model group were significantly increased （P<0.01）. Moreover， the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group， body weight， colon length and IL-10 content in each dose group of Xielitang were significantly increased （P<0.05， P<0.01）， DAI score， intestinal weight index and CMDI score， IL-6 and TNF-α contents， mRNA and protein expression levels of TLR4， NF-κB and HIF-1α were notably decreased （P<0.05， P<0.01）. The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS， and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.