Renal biopsy has been an essential part of the diagnosis and management of kidney disease. In recent years, the rapid development of artificial intelligence (AI) technology based on convolutional neural networks has significantly facilitated its utilization in nephrology. This article focuses on the research of AI in the recognition of tissue structure and pathological diagnosis of kidney biopsy. It elaborates on the identification and segmentation of kidney tissue structure and pathological features, as well as its auxiliary role in disease diagnosis across three dimensions: light microscopy, immunofluorescence, and electron microscopy. The aim is to provide a reference for the application of AI in renal pathology research and precision medicine.

In recent years, artificial intelligence has received extensive attention in the field of kidney pathology, such as identifying kidney tissue structure and evaluating the degree of lesions. Renal pathology is the gold standard for the diagnosis of renal diseases, and histochemistry staining is the prerequisite for the assessment of renal lesions. Renal biopsy is usually evaluated by various staining methods, including hematoxylin-eosin staining, periodic acid-Schiff reaction, Masson's trichrome staining and immunol staining, among that, different staining methods focus on different structures. The paper reviewed the application and progress of artificial intelligence in renal pathology, especially in different staining methods.

Objective:To investigate the effect of trifluoperazine (TFP) on the proliferation of mesangial cells through FoxO1 pathway and its protective effect on lupus nephritis (LN) mice.Methods:In vitro, MTT assay was used to detect the effect of different concentrations of trifluoperazine on the proliferation of mesangial cells. Flow cytometry was used to detect the effect of different concentrations of TFP on the mesangial cell cycle. Western blotting method (WB method) was used to detect the effect of different concentrations of TFP on the expression of FoxO1 and cyclinD1 proteins in mesangial cells, and the expression of TFP on mesangial cells, cyclinD1 and P21 after enhancing or inhibiting the expression of FoxO1. The effect of TFP on the proliferation of MRL/LPR mouse mesangial cells and the expression of FoxO1 was detected by HE staining, immunohistochemistry and WB method, and the effect of TFP on renal function in LN mice was detected by ELISA method in vivo. WB method was used to detect the effect of TFP on mesangial cell fibrosis, that is, the protein expression levels of FN and Col1. Repeated measures analysis of variance and One-way analysis of variance were used to compare measurement data between groups, and further pairwise comparisons were made using the Bonferroni method. Results:Trifluoperazine inhibits the proliferation of mesangial cells, and the interaction effects was concentration dependence and were statistically signifiant between groups, time ( Fgroup=162.58, Ftime=50.84, Finteraction=19.12, P<0.001). Flow cytometry results showed that after mesangial cells were treated with trifluoperazine at different concentrations, the percentage of cells in the G 0/G 1 phase gradually increased, while the cells in the S phase gradually decreased. This effect was dose-dependent, the difference was statistically significant ( P<0.05). Results of WB test proved that trifluoperazine inhibited the expression of cyclinD1 protein (2.17±0.34, 1.49±0.20, 1.11±0.27, 0.15±1.55, F=33.60 , P<0.001) and up-regulated the expression of FoxO1 (0.81±0.45, 2.31±0.81, 3.51±0.52, 5.13±10.07, F=35.63, P<0.001), and also in a dose-dependent patten. In vivo experimental results showed that trifluoperazine could inhibit the proliferation of mesangial cells and promote the expression of FoxO1 in mice with lupus nephritis, and the difference wsa statistically significant ( F=8.47, P=0.007). ELISA test results showed that trifluoperazine had a protective effect on renal function [serum creatinine: normal group(144±23)μmol/L, LN group (237±14)μmol/L, LN+TFP(211±36)μmol/L, Fvalue=20.47, P<0.001, urea nitrogen: normal group (22.84±0.56)μmol/L, LN group (19.99±0.92)μmol/L, LN+TFP (13.57±0.25)μmol/L, F=331.96, P<0.001] and it was proved by WB method that trifluoperazine could inhibit Fn and Col1 expression, the difference was statistically significant ( FFN=1 312.83, FCol1=171.16, P<0.001). Conclusion:Trifluoperazine blocks the mesangial cell cycle in G 0/G 1 phase by increasing the expression of FoxO1 and inhibits cell proliferation, which may have a therapeutic effect on lupus nephritis nephritis.

Objective:To prepare cisplatin-loaded anti-progastrin-releasing peptide (ProGRP) monoclonal antibody targeted nanobubbles, and to explore the proliferation inhibition effect and anti-cancer molecular mechanism of them on small cell lung cancer (SCLC).Methods:The cisplatin targeted nanobubbles were prepared by thin film hydrating method, and the physicochemical property were explored. The subcutaneous xenograft tumor models of SCLC in 10 nude mice were established, and the ultrasound molecular targeting development effect of cisplatin targeted nanobubbles was analyzed by using blank nanobubbles as control. Another 24 tumor-bearing nude mouse models were established and randomly divided into four groups: blank nanobubbles group, cisplatin group, cisplatin nanobubbles group, cisplatin targeted nanobubbles group. The tumor inhibition rate was calculated. The effect on SCLC proliferation was detected by CCK8 method. RT-PCR and Western blotting methods were used to detect SCLC proliferation related genes the P53, Rb, c-myc protein and mRNA expression level of change, the molecular regulatory mechanism was analyzed.Results:The cisplatin targeted nanobubbles were successfully prepared. The particle size was (467.3±42.3)nm, the structure was stable. The cisplatin targeted nanobubbles had a good effect of ultrasonic molecular development in SCLC xenograft.Compared with the control group, the proliferation of SCLC cells was significantly inhibited by cisplatin targeted nanobubbles. The RT-PCR and Western blotting analysis showed that compared with the control group, the mRNA and protein levels of the proliferation-related gene P53 and Rb in the cisplatin targeted nanovesicles group were significantly up-regulated, and the mRNA and protein levels of c-myc were significantly down-regulated (all P<0.05). Conclusions:The cisplatin targeted nanobubbles can inhibit the proliferation of SCLC, and may be used as a new potential targeted drug for the treatment of SCLC.

Objective:To explore the level of tibial growth plate chondrocyte mitophagy in young rats with chronic renal failure (CRF) and its effect on chondrocyte apoptosis.Methods:Male 4-week-old Sprague-Dawley rats were randomly divided into two groups according to random number table method: normal control group ( n=20, intragastric administration with distilled water) and CRF group ( n=20, given adenine suspension 150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavage for 6 weeks. The length of tibia was measured on X ray film, the width of tibia growth plate was measured and compared on histological section, and the apoptosis rate of chondrocytes in growth plate was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The growth plate chondrocytes of two groups were isolated and cultured to the third generation in vitro, and the apoptosis rate of chondrocytes was detected by TUNEL assay. The co-localization of mitochondria and autophagy lysosomes in chondrocytes was observed by double fluorescence staining. Western blotting was used to detect the level of mitochondrial marker protein translocate of the outer mitochondrial membrane-20 (Tom-20) and autophagy marker light chain-3 protein (LC-3). The mitophagy of growth plate chondrocytes was observed by transmission electron microscope. Results:Compared with the normal control group, the tibia length of CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], and the relative width of growth plate in histological section was narrower (0.56±0.19 vs 1.00±0.21, t=6.744, P<0.001). The apoptosis rate of chondrocytes in growth plate in CRF group was higher than that in the normal control group (17.2%±4.8% vs 5.1%±3.4%, t=6.505, P<0.001). The apoptosis rate of chondrocytes cultured in vitro in CRF group was higher than that in the normal control group (11.8%±6.2% vs 3.1%±1.2%, t=4.357, P<0.001). The result of double influorescence staining showed that there was co-localization between mitochondria and autophagy lysosomes in CRF group. Western blotting results showed that the levels of LC-3 protein ( t=8.944, P<0.001) and Tom-20 protein ( t=6.708, P<0.001) in CRF group were lower than those in the normal control group. Conclusion:The level of tibial growth plate chondrocyte mitophagy in young rats with CRF increases, which will lead to a decrease in the number of mitochondria, an increase in the apoptosis and a decrease in the number of chondrocytes, and eventually lead to dysplasia of tibia.

Objective:To evaluate the effect of edaravone on renal injury in rats with aldosterone-induced hypertension.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (S group), hypertension group (H group) and edaravone group (E group). The hypertension model was developed by subcutaneously embedding aldosterone osmotic pump (administration rate 0.75 μg·kg -1·h -1) for 4 weeks.After embedding osmotic pump subcutaneously, edaravone 10 mg/kg was injected via the tail vein every day for 4 consecutive weeks in E group, while normal saline 10 ml/kg was injected instead for 4 consecutive weeks in H group.BP-2010A noninvasive manometry device was used to measure the systolic pressure of tail artery before embedding osmotic pump and at 1, 2, 3 and 4 weeks after administration.After 4 weeks of administration, the 24 h urinary albumin concentration, plasma creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured, the bilateral kidneys were weighed, the right kidney weight/body weight ratio (RKW/BW) was calculated, the glomerular extramesangial matrix area/glomerular area ratio (M/G) was measured by PAS method, and the collagen volume fraction (CVF) was measured by Masson staining method, and the expression of aldosterone receptor (MCR) and type Ⅰ collagen in renal tissues was detected by Western blot. Results:Compared with group S, the systolic pressure was significantly increased, the concentrations of 24-h urinary albumin, plasma Cr and BUN were increased, the RKW/BW ratio, M/G and CVF were increased, and the expression of type Ⅰ collagen and MCR was up-regulated after embedding osmotic pump in group H ( P<0.05). Compared with group H, the systolic pressure was significantly decreased, the concentrations of 24-h urinary albumin, plasma Cr and BUN were decreased, the RKW/BW ratio, M/G and CVF were decreased, and the expression of type Ⅰ collagen and MCR was down-regulated after embedding osmotic pump in group E ( P<0.05). Conclusions:Edaravone can reduce renal injury in rats with aldosterone-induced hypertension, and the mechanism is related to down-regulation of MCR expression.

Objective:The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods:Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014-2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results:During the study period,24-hour average concentrations of ambient O3 were 47.4 μg/m3(ranging from 1.0 to 165.9 μg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95％confidence interval[CI]:1.95 to 2.32)and 5.47(95％CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74％of the risks of arrhythmias attributable to O3 exposure.Conclusion:Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Objective:To explore the effect of Wnt/β-catenin signaling pathway on growth plate development of tibial growth plate in young chronic renal failure (CRF) rats.Methods:Four-week-old male SD rats were randomly divided into control group and CRF group ( n=20/per group). Control group was intragastric administration with distilled water, and CRF group was given adenine suspension (150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavages for 6 weeks. The full length of tibia was compared between the two groups. The width of tibia proximal growth plates was measured by micro-CT scanning, and the width of the growth plate was also measured in histological sections. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. Immunohistochemical staining was used to detect the expression of collagen Ⅱ, matrix metalloproteinase 13 (MMP-13) and β-catenin in chondrocytes. Western blotting was used to detect the protein expressions of collagen Ⅱ, MMP-13 and β-catenin. Results:Compared with the control group, the tibial length of rats in the CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], the width of growth plate in micro-CT picture was more narrow [(0.72±0.22) mm vs (1.13±0.27) mm, t=5.096, P<0.001], and the relative width of the growth plate was also more narrow ( t=6.744, P<0.001) in histological sections. The results of immunohistochemistry and Western blotting showed the expressions of collagen Ⅱ in the CRF group decreased significantly ( t=8.212, P<0.001), MMP-13 ( t=13.091, P<0.001) and β-catenin ( t=7.534, P<0.001) increased significantly compared the control group in chondrocytes. Conclusion:The Wnt/β-catenin signaling pathway is highly expressed in the tibial growth plate of young rats with chronic renal failure, which leads to accelerated degeneration and differentiation of chondrocytes and a closure tendency of growth plate.

Objective:To investigate the role and mechanism of Nod-like receptor protein 3 (NLRP3) in chronic kidney disease (CKD)-related neointimal hyperplasia (NH) of vessels.Methods:Wild type C57BL/6J male mice were randomly divided into normal control group ( n=6) and experimental group ( n=18), by removal of 5/6 kidney and ligation of left common carotid artery to establish a NH model. After established successfully, the mice in NH experimental group were randomly divided into NH model group, NLRP3 inhibitor group, and drug control group ( n=6/group). C57BL/6J male mice with NLRP3 gene knockout group did not do any treatment after the establishment of NH model. After 3 weeks of feeding, the blood and vascular tissue samples of mice were collected. The pathological changes of vascular tissue samples in mice were observed by hematoxylin-eosin staining. The expressions and localization of NLRP3-related protein were observed by immunofluorescence staining. The expression of NLRP3 mRNA in vascular tissue was detected by quantitative real-time PCR. The activity of caspase-1 in vascular tissue was measured by colorimetric method. Human aortic smooth muscle cells (HASMCs) were treated with 10% uremic serum to simulate the body's internal environment during the uremic phase. NLRP3 small interfering RNA (siRNA) was transfected or NLRP3 inhibitor glibenclamide was added to the cell cultures. The expression of NLRP3 mRNA in HASMCs was detected by quantitative real-time PCR. The activity of caspase-1 in HASMCs was detected by colorimetric method. Results:Compared with the control group, the levels of serum creatinine and blood urea nitrogen were significantly increased in the NH model group (both P<0.01). The vascular histopathology showed that vascular intima thickened, vascular smooth muscle cells proliferated and hypertrophied, nuclei were deeply stained, and cells arranged disorderly and migrated to vascular intima in the experimental group. Quantitative analysis showed that the ratio of neointima to lumen increased significantly in the NH model group than that in control group ( P<0.01). Compared with the control group, the immunofluorescence staining of vascular tissue showed that the expressions of NLRP3, caspase-1, IL-18, IL-1β and proliferating cell nuclear antigen (PCNA) protein in the NH model group increased (all P<0.01), while the expression of α-SMA decreased ( P<0.01). NLRP3 was mainly located in vascular smooth muscle cells (VSMCs). VSMCs showed a synthetic phenotype. Compared with the NH model group, the expression of NLRP3, caspase-1, IL-18, IL-1β and PCNA protein in the NLRP3 inhibitor group and NLRP3 gene knockout group decreased (all P<0.01), the expression of α-SMA increased ( P<0.01), and the pathological changes of blood vessels alleviated. Compared with healthy serum group, the expression of NLRP3, IL-18, and IL-1β and bromodeoxyuridine (BrdU) uptake in uremic serum-stimulated group were increased (all P<0.01). After transfection of NLRP3 siRNA and addition of glibenclamide, the expression of NLRP3, IL-18, and IL-1β in VSMCs in uremic serum-stimulated group decreased, and BrdU intake decreased (all P<0.01). Conclusions:NLRP3 inflammatory bodies play an important role in promoting CKD-related neointimal hyperplasia of vessels, and glibenclamide can effectively reduce neointimal hyperplasia.