Pathology diagnosis is the "gold standard" for clinical disease diagnosis and treatment. Intelligent pathology image analysis has significant clinical value in improving diagnostic efficiency and ensuring consistency. This paper systematically reviews the core multiple instance learning paradigm for whole slide image analysis, and elaborates the pretraining system, core functional branches and latest advances of pathology foundation models. Taking clinical usability as the core evaluation dimension, it establishes a multi-dimensional evaluation framework, analyzes the clinical translation potential of different technical routes, and points out the core contradiction of "excellent laboratory performance but insufficient clinical usability" in current pathology foundation models. It further dissects the key clinical translation bottlenecks of pathology foundation models, outlines future application and development directions, and provides a reference for technological research and development as well as clinical translation in computational pathology.

Objective:To discuss the promotion effect of chemokine C-C motif ligand 19(CCL19)induced macrophage M1 polarization on chronic pancreatitis of the mice,and to clarify its related mechanism.Methods:Ten male C57BL/6N mice were selected,and the pancreatic acinar cells and peritoneal macrophages were extracted from these mice to construct the macrophage-acinar cell co-culture system.The co-culture system cells were divided into control group,model group,and small interfering RNA CCL19(si-CCL19)group.The morphology of the acinar cells in various groups were observed under microscope.Forty mice were randomly selected and divided into normal group and chronic pancreatitis group,and there were 20 mice in each group.HE staining was used to observe the pathomorphology of pancreatic tissue of the mice in two groups;immunofluorescence staining was used to observe the expressions of cytokeratin 19(CK19),amylase,M1 macrophage-related markers inducible nitric oxide synthase(iNOS),and F4/80 in pancreatic tissue of the mice in two groups and morphology of follicular cells and the expressions of CK19,amylase in the co-culture system cells in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β in serum of the mice in two groups and in the co-culture system cells in various groups;immunohistochemistry was used to observe the expression of CCL19 protein in pancreatic tissue of the mice in two groups;Western blotting method was used to detect the expression levels of CCL19 protein and two nuclear factor-κB(NF-κB)signaling pathway-related proteins P65,phosphorylate P65(p-P65),kappa B inhibitor of kinase α/β(IKKα/β),phosphorylated IKKα/β(p-IKKα/β),IkBα,phosphorylated IκBα(p-IκBα)in pancreatic tissue of the mice in two groups and in the co-culture system cells in various groups.Results:The HE staining results showed that the acinar cells in pancreatic tissue of the mice in normal group were tightly arranged;compared with normal group,the acinar cells of the mice in chronic pancreatitis group showed obvious vacuolation and acinar cell ductal metaplasia,indicating successful preparation of the mouse pancreatitis model.The immunofluorescence staining results showed that compared with control group,the acinar cells in model group exhibited severe vacuolation,the CK19 expression was significantly increased,and the amylase expression was significantly decreased;compared with model group,the acinar cell ductal metaplasia in si-CCL19 group was decreased,the CK19 expression was significantly decreased,and the amylase expression was significantly increased;compared with normal group,the expression of amylase in pancreatic tissue of the mice in chronic pancreatitis group was significantly decreased,while the expressions of CK19 and M1 macrophage markers iNOS and F4/80 were significantly increased.The ELISA results showed that compared with normal group,the serum levels of TNF-α,IL-6,and IL-1β of the mice in chronic pancreatitis group were significantly increased(P<0.05);compared with control group,the levels of TNF-α,IL-6,and IL-1β in the cells in model group were significantly increased(P<0.05);compared with model group,the levels of TNF-α,IL-6,and IL-1β in the cells in si-CCL19 group were significantly decreased(P<0.05).The immunohistochemistry results showed that compared with normal group,the expression of CCL19 protein in pancreatic tissue of the mice in chronic pancreatitis group was significantly increased.The Western blotting results showed that compared with normal group,the expression levels of CCL19 protein and NF-κB signaling pathway-related proteins p-P65,p-IKKα/β,and p-IκBα in pancreatic tissue of the mice in chronic pancreatitis group were significantly increased(P<0.05);compared with control group,the expression levels of CCL19,p-IKKα/β,p-P65,and p-IκBα proteins in the cells in model group were significantly increased(P<0.05);compared with model group,the expression levels of CCL19,p-IKKα/β,p-P65,and p-IκBα proteins in the cells in si-CCL19 group were decreased(P<0.05).Conclusion:CCL19 promotes the macrophage M1 polarization through the NF-κB signaling pathway,induces the formation of inflammatory microenvironment,and promotes the occurrence and development of pancreatitis.

Objective:To investigate the influencing factors of breakthrough cancer pain (BTcP) in patients with advanced pancreatic cancer.Methods:According to the inclusion and exclusion criteria, patients with advanced pancreatic cancer who were diagnosed and followed up by outpatient service in the 909th Hospital of the Joint Logistic Support Force from January 2019 to December 2020 were prospectively selected as the study subjects. According to whether breakthrough cancer pain occurred, all patients were divided into observation group (breakthrough cancer pain) and control group (no breakthrough cancer pain). The relevant clinical data of the included patients including age, gender, presence or absence of vomit, constipation, sleep disruption, frequency of basic pain every week, with or without regular medication, heavy physical labor, with or without vascular invasion, bone metastasis, abdominal metastasis and lung metastasis, as well as whether surgery, radiotherapy or chemotherapy were collected and the data of evaluation indicators during follow-up were recorded. Digital pain score (NRS) and visual analog score (VAS) were used as pain evaluation score. Univariate and logistic regression were used to analyze the related influencing factors of breakthrough cancer pain. Receiver operating characteristic curve (ROC) was drawn, and area under curve (AUC), sensitivity and specificity were calculated to analyze the predictive value for breakthrough cancer pain.Results:A total of 173 patients were included in the study, with 49 cases in the observation group and 124 cases in the control group. Univariate analysis showed that aged ≥50 years old, constipation, sleep disruption, frequency of basic pain ≥3 times, irregular medication, heavy physical labor, bone metastasis, lung metastasis, radiochemotherapy, high NRS score and high VAS score were the influencing factors for breakthrough cancer pain (all P value <0.05). Multivariate analysis showed that irregular medication ( OR=1.879, 95% CI 2.473-4.757, P=0.002), basal pain ≥3 times ( OR=2.067, 95% CI 1.364-6.825, P=0.004), bone metastasis ( OR=2.756, 95% CI 1.153-5.846, P<0.001), NRS score ( OR=3.787, 95% CI 2.647-5.958, P<0.001), VAS score ( OR=2.684, 95% CI 1.545-7.878, P<0.001), were the risk factors for breakthrough cancer pain. The AUC of NRS score for predicting the occurrence of breakthrough cancer pain was 0.665 (95% CI0.573-0.757, P=0.001), and the cut-off value was 2.5 score with a sensitivity of 61.2% and a specificity of 77.1%. The AUC for predicting breakthrough cancer pain by VAS score was 0.608 (95% CI0.515-0.701, P=0.028), and the cut-off value was 2.5 score with a sensitivity of 67.9% and a specificity of 63.7%. The AUC of NRS+ VAS score for predicting breakthrough cancer pain was 0.692 (95% CI0.604-0.780), and the cut-off value was 4.5 score with a sensitivity of 81.6% and a specificity of 79.8%. Conclusions:Patients with advanced pancreatic cancer have a high incidence of breakthrough cancer pain, which was related to a variety of factors. NRS combined with VAS score can effectively predict the occurrence of breakthrough cancer pain.

[This corrects the article DOI: 10.1016/j.jpha.2021.06.007.].

GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana.However,information regarding its structure,biological activities,and related mechanisms is not entirely available.A series of spectroscopic analyses,structural degradation,interconversion,and crystallography were performed to identify the structure of GB7 acetate.The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells.The expressions of the related proteins were measured by Western blotting.Transmission electron microscopy(TEM),acridine orange(AO)and monodansylcadaverine(MDC)staining were used to detect the presence of autophagic vesicles and autolysosomes.A transwell assay was performed to demonstrate metastatic capabilities.Oxygen consumption rate(OCR)and extracellular acidification rate(ECAR)assays were performed to determine the mitochondrial oxidative phosphorylation(OXPHOS)and glycolysis activity of HCT 116 cells.The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells.Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes.GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate(AMP)-activated pro-tein kinase α(p-AMPKα),which are key elements of autophagy.In addition,GB7 acetate suppressed the metastatic capabilities of HCT 116 cells.Additionally,the production of matrix metallo-proteinase-2(MMP-2)and MMP-9 was reduced,whereas the expression of E-cadherin(E-cad)was upregulated.Furthermore,GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis.In conclusion,the structure of the novel Galbulimima alkaloid GB7 acetate was identified.GB7 acetate was shown to have anti-proliferative,pro-autophagic,anti-metastatic,and anti-metabolite capabilities in HCT 116 cells.This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.

PurposeTo investigate the image quality of Dual Source CT (DSCT) high pitch prospective scan in acute chest pain examination by using triple-rule-out (TRO) protocol and its responses to heart beat rate change.Materials and Methods Thirty-two consecutive patients who planned to undergo TRO acute chest pain examination were enrolled and randomly divided into research group and control group. The conventional retrospective spiral scanning protocol was applied to the patients in the control group, while the high pitch prospective spiral scanning mode was used in the research group. CT value, noise level, SNR, CNR and radiation dosage in aorta and pulmonary arteries were recorded and compared between the two groups, and the image quality of the coronary arteries was scored subjectively.Results No significant difference was found in the aspects such as CT value, noise level, SNR, CNR radiation dosage in aorta and pulmonary arteries (P>0.05); however, the subjective scoring for coronary artery in the research group (85.5%) was significantly lower than that in the control group (93.9%) (χ2=8.33,P<0.05). Considering the influence of severe heart rate changes, we excluded those patients whose heart rate variance was more than 5 beats/min (control group:n=5; research group:n=4) and then compared the image quality of the two groups again. The subsequent results showed no difference (χ2=0.12,P>0.05). In addition, the radiation dosage in the control group was significantly higher than that in the research group [(20.8±6.2) mSvvs. (2.3±0.4) mSv;t=17.142,P<0.01].Conclusion DSCT high pitch prospective scanning in TRO protocol shows high success rate in examining patients with acute chest pain whose heart beat rate is lower than 80 beats/min and heart beat variance is less than 5 beats/min. The image quality has no difference with that derived from retrospective scan but with far more less radiation dose (2.3±0.4) mSv. This method thus is promising and can be widely promoted clinically.

A new biosensor was prepared based on conductive polymer poly ( 3 , 4-ethylenedioxythiophene ) ( PEDOT) and 1-pyrenebutanoic acid ( PBA) through π-π stacking, as well as hematin associated with PBA through coordinate bonds of Zr4+ and carboxyl group. Its stability and sensitivity were examined by cyclic voltammetry ( CV) , electrochemical impedance spectroscopy ( EIS) and current-time ( i-t) method. A pair of well defined and quasi-reversible redox peaks was observed when GCE/PEDOT/PBA/hematin was tested by CV in PBS without oxygen. The electron transfer rate constant was estimated to be 4. 8 s-1 . Results indicated that the PEDOT film enhanced the electron transfer process of hematin. When the i-t method was used to detect the response of biosensor to catechol with different concentrations, it displayed a linear response for the reduction of catechol in the range of 0. 5-200 μmol/L. The linear equation was i=0. 018C+0. 006 ( R=0. 9998), and the detection sensitivity was 0. 258 μA (μmol/L· cm2) with a detection limit of 0. 33 nmol/L (S/N=3). The results illustrate that the GCE/PEDOT/PBA/hematin biosensor is very sensitive and stable.

Objective To discuss the clinical value of application of three-dimensional reconstruction technique of MSCT in examination of colonic tumours.Methods Thirty patients underwent scanning using helical CT and post-processing on the workstation.All CTC images were reconstructed using shaded surface display (SSD) on workstation.Perspestive images such as the ones from DCBE were generated via raysum.The images could clearly demonstrate the extent and detail of the disorder by adjusting the CT value threshold.These results and that of barium enema and colon endoscopy were compared.Results Thirty cases had completely clinical and pathological data.3D images could correctly reveal the macroscopic morphology of colon tract and location of lesions.The correctly diagnostic rate was 100％ by MSCT,while the diagnostic rate by CTVE and colon endoscopy was basicly identical.Conclusion With the utilization of multiple methods,3D reconstruction can effectively demonstrate colonic tumours,and can be applied routinely in examination of colonic tumours.

Objective To investigate the roles of cardiac activity index(Tei index) on evaluation the right ventricular function after neonatal asphyxia.Methods Sixty neonatal asphyxia who included 35 cases of mild asphyxia(mild asphyxia group) and 25 cases of severe asphyxia(severe asphyxia group) and 30 cases of normal full-term newborns(control group) were selected.Echocardiographic examinations were performed on 24-48 h after birth,which included pulmonary artery systolic pressure (PASP),right ventricular ejection fraction(RVEF),tricuspid early diastolic peak(peak E) and late diastolic peak(peak A),and E/A ratio was acquired.The right ventricular cardiac activity index (RV-Tei index) was measured by Doppler spectrum.Results There was no significant difference in RVEF,E/A ratio among mild asphyxia group,severe asphyxia group and control group (P ＞ 0.05).RV-Tei index in mild asphyxia group and severe asphyxia group was increased compared with that in control group (0.489 ± 0.090,0.625 ± 0.100 vs.0.345 ± 0.120),and there was significant difference (P＜ 0.05 or ＜0.01).There was significant difference in RV-Tei index between mild asphyxia group and severe asphyxia group (P ＜ 0.05).RV-Tei index in neonatal asphyxia was positively correlated with PASP (r =0.950,P ＜ 0.05),and there was no relationship between RV-Tei index and gestational age,weight,heart rate (r =-0.068,-0.280,-0.360,P ＞0.05).Conclusions Neonatal asphyxia can lead to disorders of the right ventricular function.Tei index can evaluate early overall changes of the right ventricular function and is better than conventional ultrasound technology in neonatal asphyxia.

OBJECTIVE: To explore the clinical characteristics and treatment effect of adenoid cystic carcinoma in nasal cavity and sinuses. METHOD: Sixteen of all 18 cases of adenoid cystic carcinoma of nasal cavity and sinuses were performed operation and radiotherapy. Other 2 cases were performed radiotherapy. RESULT: Eighteen cases of patients were followed up for 5 years. Eight patients with early stage had no death. Five in 10 cases of advanced patients died, one case was out of following-up. In 11 of high differentiation group, 1 case died. In 7 of lower differentiation group, 4 cases died, 1 case lost. CONCLUSION Adenoid cystic carcinomas of nasal cavity and sinuses are distinct clinicopathological category and the clinical symptoms are noncharacteristic. Paying attention to the differential diagnosis and promoting related knowledge can help to avoid misdiagnosis. The prognosis is related to pathological category and clinical stage. High stage and high invasion of adenoid cystic carcinoma lead to poor prognosis.
Adult ; Aged ; Carcinoma, Adenoid Cystic ; pathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Nasal Cavity ; pathology ; Nose Neoplasms ; pathology ; therapy ; Paranasal Sinuses ; pathology