[Accelerating the construction of digital and intelligentialized pathology and the prospects].

With the continuous development of informatization, digitalization and artificial intelligence technology, the working mode of the pathology department has gradually changed from the traditional manual check, paper circulation and physical carrier storage to the informatization process and digital storage. The traditional pathology discipline has ushered in unprecedented opportunities and challenges. Digital pathology department also emerge as the times require. Simultaneously, with the full integration of artificial intelligence technology in pathology department, the concept of "department of digital and intelligentialized pathology" was proposed. Based on information and digital technology, the digital intelligent pathology department integrates intelligent management system, optimizes the previous cumbersome management and workflow of the pathology department, develops advanced technologies such as intelligent material extraction, unmanned organization processing, artificial intelligence quality control, artificial intelligence diagnosis, and promotes the intelligent construction of the pathology department.

Development and validation of a multiphase CT radiomics nomogram for the preoperative prediction of lymphovascular invasion in patients with gastric cancer.

AIM: To develop a nomogram to predict lymphovascular invasion (LVI) in gastric cancer by integrating multiphase computed tomography (CT) radiomics and clinical risk factors. MATERIALS AND METHODS: One hundred and seventy-two gastric cancer patients (121 training and 51 validation) with preoperative contrast-enhanced CT images and clinicopathological data were collected retrospectively. The clinical risk factors were selected by univariate and multivariate regression analysis. Radiomic features were extracted and selected from the arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images of each patient. Clinical risk factors, radiomic features, and integration of both were used to develop the clinical model, radiomic models, and nomogram, respectively. RESULTS: Radiomic features from AP (n=6), VP (n=6), DP (n=7) CT images and three selected clinical risk factors were used for model development. The nomogram showed better performance than the AP, VP, DP, and clinical models in the training and validation datasets, providing areas under the curves (AUCs) of 0.890 (95% CI: 0.820-0.940) and 0.885 (95% CI:0.765-0.957), respectively. All models indicated good calibration, and decision curve analysis proved that the net benefit of the nomogram was superior to that of the clinical and radiomic models throughout the vast majority of the threshold probabilities. CONCLUSIONS: The nomogram integrating multiphase CT radiomics and clinical risk factors showed favourable performance in predicting LVI of gastric cancer, which may benefit clinical practice.

[Efficacy of sacubitril/valsartan in peritoneal dialysis patients with HFpEF and its effect on residual renal function].

Objective: To investigate the efficacy of sacubitril/valsartan in peritoneal dialysis (PD) patients with heart failure with preserved ejection fraction (HFpEF) and its effect on residual renal function. Methods: PD patients with HFpEF in Ningbo First Hospital from March 2018 to August 2021 were retrospectively enrolled and divided into study group with sacubitril/valsartan and control group with valsartan. The clinical baseline data before treatment and clinical indicators during follow-up (6 and 12 months after treatment) were collected and compared between the two groups, and the adverse reactions were also recorded. Results: A total of 99 patients were included in the study. There were 61 patients in the study group, including 44 males and 17 females, with a mean age of (52±13) years. Meanwhile, there were 38 patients in the control group, including 23 males and 15 females, with a mean age of (57±14) years. There was no statistically significant difference in clinical baseline data between the two groups (e.g., age, sex, body mass index, duration of dialysis) (all P>0.05). The N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular end-systolic dimension (LVDs) were lower, but the left ventricular ejection fraction (LVEF) was higher in the study group than those in the control group at 6 and 12 months after treatment (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were lower than baseline values at 6 and 12 months after treatment respectively, with statistically significant differences (all P<0.05). However, there were no statistically significant differences in the decreases of SBP and DBP between the two groups at 6 and 12 months after treatment (all P>0.05). The decrease extents in residual estimated glomerular filtration rate (eGFR) [0.52 (-0.05, 1.19) vs 1.72 (0.97, 2.39) ml·min-1·(1.73 m2)-1, P<0.001]and 24-h residual urine volume [200 (-100, 300) vs 300 (137, 400) ml, P=0.018] at 12 months after treatment were lower in the study group than those in the control group. During the follow-up period, hyperkalemia occurred in 16 cases (26.2%) and 13 cases (34.2%) in the study group and the control group, and hypotension occurred in 3 cases (4.9%) and 1 case (2.6%) in the study group and the control group, respectively. There were no adverse reactions such as cough and angioneurotic edema in the two groups. Conclusions: Sacubitril/valsartan can safely and effectively improve cardiac function and lower blood pressure in PD patients with HFpEF. Compared with valsartan, sacubitril/valsartan may be more beneficial to delay the loss of residual renal function in PD patients with HFpEF.

[Proliferative lesions with mesonephric features in the gynecologic tract: a clinicopathological analysis of sixteen cases].

Objective: To investigate the clinicopathological features of proliferations with mesonephric features (PMF) of the gynecologic tract. Methods: A retrospective analysis was performed on the clinical and pathological data of 16 cases with PMF that were diagnosed from October 2016 to January 2022 at a single institution. The relevant literature was reviewed. Results: Among the 16 cases, with an average of 53 years (31-68 years), there were 5 cases of mesonephric hyperplasia, 4 cases of mesonephric adenocarcinoma and 7 cases of mesonephric-like adenocarcinoma. The five cases of mesonephric hyperplasia were located in the lateral wall of the cervix and composed of simple tubules with growth patterns of diffuse or lobular clusters, without obvious stromal reaction. Four cases of mesonephric adenocarcinoma consisted of a mixture of papillary, cribriform, solid and other architectures, the nuclei resembling these of papillary thyroid carcinoma, and strong fibroproliferative reaction. They were located deep in the cervical and vaginal stroma. One of the tumors showed atypical mesonephric hyperplasia adjacent to the tumor. Five uterine and two ovarian mesonephric-like adenocarcinoma cases had similar histological morphology with mesonephric adenocarcinoma, but no mesonephric remnants/mesonephric hyperplasia were found near the tumors. In addition, four (4/5) uterine mesonephric-like adenocarcinoma cases originated from the endometrium with secondary involvement of myometrium, including one case with clear demarcation between the normal endometrium and the neoplastic glands. One (1/5) uterine mesonephric-like adenocarcinoma case was mainly located in the deep myometrium, along with adenomyosis around the tumor, without mesonephric remnants. Two ovarian mesonephric-like adenocarcinoma cases were associated with endometriotic cyst/endometrioid cystadenoma, including one case with an abrupt transition between normal epithelium and atypical mesonephric cells within the single individual cyst directly adjacent to tumor. All mesonephric hyperplasia and mesonephric adenocarcinoma cases were positive for GATA3, PAX8 and CD10 in a varying degree, and negative for ER, PR and TTF1. Although mesonephric-like adenocarcinoma showed a considerable overlap of immunohistochemical expression with mesonephric adenocarcinoma, seven mesonephric-like adenocarcinoma cases were positive for TTF1 and negative for GATA3. Conclusions: PMF is a class of rare proliferative lesions with morphological and immunophenotypic characteristics of mesonephric duct. Its commonly involved site, microscopic morphology, associated benign and/or atypical lesions, and immunophenotype may contribute to its diagnosis and differential diagnosis.

[The urate-lowering efficacy of febuxostat and its relationship with residual renal function in peritoneal dialysis patients with hyperuricemia].

Objective: To investigate the urate-lowering efficacy of febuxostat in peritoneal dialysis (PD) patients with hyperuricemia (HUA) and its relationship with residual renal function. Methods: Patients with HUA who underwent PD in Ningbo First Hospital from January 2018 to October 2021 were enrolled and divided into experimental group and control group according to whether to use febuxostat. The clinical baseline data before treatment and clinical indicators during 1-12 months after treatment were collected in two groups, and the adverse reactions during the use of febuxostat were also recorded. The changes of serum uric acid, standard-reaching rate and residual renal function were compared between the two groups during the follow-up. Results: A total of 105 patients were included in the study. There were 55 patients in the experimental group [27 males and 28 females, with a mean age of (54.5±14.8) years] and 50 patients in the control group [32 males and 18 females, with a mean age of (53.8±15.2) years]. No statistically significant difference was detected in clinical baseline data between the two groups (all P>0.05). The serum uric acid of the experimental group [(479±77), (311±69), (286±61), (307±65), (312±57) µmol/L] and control group [(486±59), (454±71), (453±76), (463±70), (459±76) µmol/L] were lower than baseline values at 1, 3, 6 and 12 months after treatment and the differences of two groups were statistically significant (all P<0.05). The serum uric acid in experimental group was significantly lower than that of control group (P<0.05). At 1, 3, 6 and 12 months after treatment, the standard-reaching rate of serum uric acid in the experimental group was significantly higher than that of the control group (all P<0.05). The decrease of residual estimated glomerular filtration rate (eGFR) and residual renal urea clearance index (Kt/V) in the experimental group were significantly lower than those in the control group at 12 months after treatment (all P<0.05). During the follow-up, the incidence of adverse reactions in the experimental group was 9.09% (5/55). Conclusions: Febuxostat can effectively treat PD patients with hyperuricemia and has a high safety profile. Moreover, it may delay the loss of residual renal function.

[Next-generation diagnostic pathology].

With the technological progresses and applications of human genome sequencing, bioinformatics analysis and data mining, and molecular pathology and artificial intelligence-assisted pathological diagnosis, the development of clinical medicine is moving towards the era of precision diagnosis and treatment. In the context of this era, the traditional diagnostic pathology is facing unprecedented opportunities and challenges in our history and is striving towards the "next-generation diagnostic pathology" (NGDP). NGDP is based on histomorphology and clinical data, and characterized by the combination of molecular detection and bioinformatics analysis, intelligent sampling and process quality control, intelligent diagnosis and remote consultation, lesion visualization and "non-invasive" pathology as well as other innovative cutting edge interdisciplinary technologies. The NGDP reports will include the results from multi-omics and cross-scale integrated diagnosis for final diagnosis. NGDP will also be applied for predicting disease progression and outcomes, and determining optional therapeutics as well as assessing treatment responses, so that a novel "golden standard" of disease diagnosis can be established. In the near fature, it is necessary to stimulate the innovative vitality of pathology disciplines, accelerate the maturity and application for NGDP, update the theory and technical system of pathology, and perform its important applicable role in the prevention, diagnosis, treatment of diseases so that the futher development of clinical medicine will be promoted and the strategy for maintenance of being healthy in China will be served.

Euglycemic diabetic ketoacidosis following major vascular surgery is a new item on the differential for postoperative acidosis.

New pharmacologic advances in the treatment of diabetes include SGLT-2 inhibitors, which have been demonstrated in randomized-controlled clinical trials to reduce overall and cardiac-specific mortality and slow progression of chronic kidney disease. Euglycemic diabetic ketoacidosis is a rare but life-threatening complication associated with the use of SGLT-2 inhibitors. Here we describe a case of severe euglycemic diabetic ketoacidosis after lower extremity bypass in a patient taking an SGLT-2 inhibitor. Awareness of this potential complication is essential as these novel agents are increasingly used in patients with cardiovascular disease.

Ivy Sign in Moyamoya Disease: A Comparative Study of the FLAIR Vascular Hyperintensity Sign Against Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: The ability of the ivy sign on contrast-enhanced T1-weighted MR imaging (CEMR) to reflect cerebral perfusion and postoperative revascularization in Moyamoya disease remains largely unknown. We aimed to compare the capabilities of CEMR and FLAIR. MATERIALS AND METHODS: CEMR, FLAIR, arterial spin-labeling, and DSA were performed in 44 patients with Moyamoya disease. The ivy sign was scored separately on CEMR and FLAIR using the Alberta Stroke Program Early CT Score. The status of leptomeningeal collaterals was scored on DSA. The postoperative Matsushima grade was evaluated at least 3 months after surgical revascularization. RESULTS: Scoring of the ivy sign on CEMR showed excellent interrater reliability, and FLAIR vascular hyperintensity showed moderate interrater reliability. Correlation analyses revealed that DSA scores were more consistent with the CEMR-based ivy sign score (r = 0.25, P = .03) than with FLAIR vascular hyperintensity (r = 0.05, P = .65). The CEMR-based ivy sign score was significantly correlated with CBF in late-Suzuki stage Moyamoya disease (t = -2.64, P = .02). The CEMR-based ivy sign score at baseline was significantly correlated with the postoperative Matsushima grade (r = 0.48, P = .03). CONCLUSIONS: In this study, CEMR outperformed FLAIR in capturing the ivy sign in Moyamoya disease. In addition, the CEMR-based ivy sign score provided adequate information on hemodynamic status and postoperative neovascularization. The current study suggested that CEMR could be considered as an alternative to FLAIR in future studies investigating leptomeningeal collaterals in Moyamoya disease.

The expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells.

OBJECTIVE: To investigate the expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells. PATIENTS AND METHODS: Samples of lung cancer tissue (55 cases) and pericarcinomatous tissue (55 cases) were collected in thoracic surgery in our hospital from May 2017 to November 2018. The expression levels of miR-151a-5p and miR-23b in lung cancer tissues and pericarcinomatous tissues were detected by RT-PCR. Lung cancer cells A549 were transfected. Before transfection, the cells were divided into a negative control group (NC group, transfected with miRNA NC), a group transfected with miR-151a-5p inhibitor and a group transfected with miR-23b inhibitor. MTS Cell Proliferation Colorimetric Assay Kit (CCK8) was used to detect cell proliferation and draw the growth curve. Transwell chamber was used to detect the invasion ability in vitro, and BD flow cytometry was used to detect apoptosis in each group. RESULTS: The expression levels of miR-151a-5p and miR-23b in lung cancer tissues were significantly higher than those in pericarcinomatous tissues (p<0.001). After 48 h to 72 h, the cell growth of both the miR-151a-5p inhibitor group and the miR-23b inhibitor group was significantly lower than that of the NC group (p<0.001). The numbers of invasion of miR-151a-5p inhibitor group and miR-23b inhibitor group were significantly lower than that of NC group (p<0.00). The apoptosis rates of miR-151a-5p inhibitor group and miR-23b inhibitor group were significantly higher than that of NC group (p<0.001). CONCLUSIONS: Both miR-151a-5p and miR-23b are highly expressed in lung cancer, and the inhibition of miR-151a-5p and miR-23b can restrain the proliferation, invasion and migration of lung cancer A549 cells, thereby promoting the apoptosis of lung cancer A549 cells.

[A pathological report of three COVID-19 cases by minimal invasive autopsies].

Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

[High-intensity focused ultrasound in the treatment of glaucoma].

In recent years, with the improvement of high-intensity focused ultrasound technology, ultrasound cycloplasty has once again gained clinical recognition, becoming one of the non-invasive procedures for glaucoma treatment. Although high-level evidence is still lacking so far, the existing literature has shown that ultrasound cycloplasty can effectively and safely decreases the intraocular pressure in glaucoma by reducing the formation of aqueous humor and increasing the drainage of aqueous humor through the uveoscleral pathway. This article focuses on the efficacy and safety of ultrasound cycloplasty in the treatment of glaucoma, reviews the existing literature, and summarizes the information on the development of equipment, treatment mechanisms, surgical procedures, effectiveness of intraocular pressure reduction, and post-operative complications, with the purpose to provide reference for clinical research and application. (Chin J Ophthalmol, 2020, 56: 66-70).

Modeled changes to the Great Plains low-level jet under a realistic irrigation application.

Low-level jets (LLJs) are relatively fast-moving streams of air that form in the lower troposphere and are a common phenomenon across the Great Plains (GP) of the United States. LLJs play an important role in moisture transport and the development of nocturnal convection in the spring and summer. Alterations to surface moisture and energy fluxes can influence the planetary boundary layer (PBL) development and thus LLJs. One important anthropogenic process that has been shown to affect the surface energy budget is irrigation. In this study, we investigate the effects of irrigation on LLJ development across the GP by incorporating a dynamic and realistic irrigation scheme into the Weather Research and Forecasting (WRF) model. WRF simulations were conducted with and without the irrigation scheme for the exceptionally dry summer of 2012 over the GP. The results show irrigation-introduced changes to LLJ features both over and downstream of the most heavily irrigated regions in the GP. There were statistically significant increases to LLJ speeds in the simulation with the irrigation parameterization. Decreases to the mean jet core height on the order of 50 m during the overnight hours were also simulated when irrigation was on. The overall frequency of jet occurrences increased over the irrigated regions by 5-10%; however, these differences were not statistically significant. These changes were weaker than those reported in earlier studies based on simple representations of irrigation that unrealistically saturate the soil columns over large areas over a long period of time, which highlights the importance and necessity to represent human activity more accurately in modeling studies.

Biosorption of lead(II) from aqueous solution by lactic acid bacteria.

The biosorption of Pb(II) from aqueous solutions by lactic acid bacterium, Lactobacillus brevis, was studied. The effects of initial pH, contact time, initial Pb(II) concentration, bacterial concentration, rotation speed and temperature of biosorption of Pb(II) from aqueous solutions were investigated. The optimal condition for Pb2+ ions adsorption was observed at pH 6, with the rotational speed of 120 rpm.min-1, bacterial concentration of 3 g.L-1, temperature of 40 °C and contact time of 12 h. The correlation regression coefficients showed that the biosorption process can be well fitted with the Redlich-Peterson, Langmuir, Freundlich and Temkin isotherm models. The equilibrium adsorption capacity reached 53.632 mg.g-1. Binding energy value was 0.264 kJ/mol, which indicated that the adsorption process seemed to involve chemisorption and physisorption. Kinetics of adsorption was found to fit well with the pseudo-second-order and Elovich kinetic equations. Thermodynamic parameters revealed the feasibility, spontaneity and endothermic nature of adsorption.

Association between extrauterine growth restriction and changes of intestinal flora in Chinese preterm infants.

The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.

[Spectomycin B1 induces VEGFR2 de-SUMO modification to inhibit angiogenesis in nasopharyngeal carcinoma].

Objective:To explore the new mechanism of spectomycin B1 in inhibiting angiogenesis of nasopharyngeal carcinoma and to provide a theoretical basis for targeted gene therapy of nasopharyngeal carcinoma. Method:Human nasopharyngeal carcinoma CNE1 cells were divided into two groups, the control group and spectomycin B1 group. Western blot was used to detect the expression levels of small ubiquitin-related modified protein（SUMO） 1 and vascular endothelial growth factor receptor 2（VEGFR2）. The angiogenesis assay was used to detect the angiogenic ability of CNE1 cells, and the apoptosis was detected by flow cytometry. The model of nasopharyngeal carcinoma-bearing mice was established, spectomycin B1 was administered, tumor volume and weight were measured, and protein expression of CD31 was detected by immunohistochemistry and microvessel density was compared. Result:Spectomycin B1 could reduce deSUMOylation of VEGFR2 protein by 4.05 times, significantly reduce the angiogenic ability of CNE1 cells, and increase the apoptosis rate by 20.68%. In the tumor-bearing mouse model, spectomycin B1 treatment could inhibit subcutaneous tumor growth rate and weight, and the blood vessel density decreased by 40.04%. Conclusion:Spectomycin B1 can inhibit neovascularization of nasopharyngeal carcinoma by inducing deSUMOylation of VEGFR2 protein.