Objective:To explore the effect and mechanism of Chlorfortunone A(ChlA) in the treatment of diabetic nephropathy(DN) in mice.Methods:The DN model mice were assigned to DN, low-dose ChlA(ChlAL) and high-dose ChlA(ChlAH), and the normal control groups(Ctrl). Kidney tissue was analyzed via HE and Masson staining, and urine albumin, fasting blood glucose and kidney weight were measured. Collagen1 and α-SMA proteins were detected in renal tissues. The level of GSH-px, SOD, CAT, and TGF-β were detected. The TGF-β/Smad2 pathway in kidney tissue was detected. The mechanism was verified by setting the high glucose+ ChlA+ TGF-β group in MPC-5 cells. The proliferation of the cells and DCFDA staining were detected.Results:Compared to the Ctrl group, the DN group had significantly higher UACR and kidney weight( P<0.001). High-dose ChlA reduced UACR and kidney weight( P<0.05), with no effect on blood glucose( P>0.05). Masson staining showed reduced fibrosis with ChlA treatment. Collagen I and α-SMA expressions were significantly higher in DN( P<0.001) and decreased with ChlA treatment( P<0.05). GSH-px, SOD, and CAT levels were lower in DN( P<0.001), while TGF-β was elevated( P<0.001); ChlA increased antioxidant enzymes and decreased TGF-β( P<0.05). The TGF-β/Smad2 pathway was upregulated in DN( P<0.001) and inhibited by ChlA( P<0.001). In vitro, ChlA reduced cell proliferation( P<0.05) and increased ROS levels( P<0.001). Conclusions:ChlA alleviates kidney injury and fibrosis in DN mice, reduces oxidative stress, which may be related to the inhibition of the TGF-β/Smad2 pathway.

Objective:To explore the effect and mechanism of Chlorfortunone A(ChlA) in the treatment of diabetic nephropathy(DN) in mice.Methods:The DN model mice were assigned to DN, low-dose ChlA(ChlAL) and high-dose ChlA(ChlAH), and the normal control groups(Ctrl). Kidney tissue was analyzed via HE and Masson staining, and urine albumin, fasting blood glucose and kidney weight were measured. Collagen1 and α-SMA proteins were detected in renal tissues. The level of GSH-px, SOD, CAT, and TGF-β were detected. The TGF-β/Smad2 pathway in kidney tissue was detected. The mechanism was verified by setting the high glucose+ ChlA+ TGF-β group in MPC-5 cells. The proliferation of the cells and DCFDA staining were detected.Results:Compared to the Ctrl group, the DN group had significantly higher UACR and kidney weight( P<0.001). High-dose ChlA reduced UACR and kidney weight( P<0.05), with no effect on blood glucose( P>0.05). Masson staining showed reduced fibrosis with ChlA treatment. Collagen I and α-SMA expressions were significantly higher in DN( P<0.001) and decreased with ChlA treatment( P<0.05). GSH-px, SOD, and CAT levels were lower in DN( P<0.001), while TGF-β was elevated( P<0.001); ChlA increased antioxidant enzymes and decreased TGF-β( P<0.05). The TGF-β/Smad2 pathway was upregulated in DN( P<0.001) and inhibited by ChlA( P<0.001). In vitro, ChlA reduced cell proliferation( P<0.05) and increased ROS levels( P<0.001). Conclusions:ChlA alleviates kidney injury and fibrosis in DN mice, reduces oxidative stress, which may be related to the inhibition of the TGF-β/Smad2 pathway.

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.

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.

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 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.