Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.

Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.

Objective To investigate the protective effect of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI), and to clarify the critical role and regulating mechanism of transient receptor potential canonical (TRPC) 6/poly adenosine-diphosphate-ribose polymerase (PARP) 1 signaling pathway during this process. Methods The hucMSC-Exo was extracted by ultracentrifugation, and identified by transmission electron microscope (TEM), nanoparticle tracing analysis and Western blot. SD rats were randomly divided into the sham operation group (group S), sham operation+TRPC6 inhibitor SKF96365 group (group SS), renal IRI group (group IRI), exosome treatment group (group EXO) and exosome +TRPC6 inhibitor SKF96365 group (group ES), with 6 rats in each group. Serum creatinine and blood urea nitrogen levels were detected. Pathological changes of renal tissues were observed by hematoxylin-eosin (HE) staining and Paller score was calculated. The expression levels of key molecules of necroptosis in rat renal tissues, including receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL), TRPC6 and PARP1, were detected by Western blot. Results Typical saucer-like structure was observed under TEM. Nanoparticle tracing analysis showed that the average diameter of the extracted substance was 125.9 nm. Western blot revealed that the surface markers of CD9, CD63 and CD81 were positively expressed, confirmed that the extracted substance was exosome. Compared with group S, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was worsened, Paller score was elevated, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group IRI (all P < 0.05). Compared with group IRI, the serum creatinine and blood urea nitrogen levels were down-regulated, the pathological damage of renal tissues was mitigated, Paller score was decreased, the relative expression levels of TRPC6 and PARP1 proteins were up-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were down-regulated in group EXO (all P < 0.05). Compared with group EXO, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was aggravated, Paller score was increased, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group ES (all P < 0.05). Conclusions hucMSC-Exo may alleviate the necroptosis induced by renal IRI in rat models, which is related to the activation of TRPC6/PARP1 signaling pathway.

Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca²⁺ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca²⁺ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation

Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.

Objective To investigate the imaging features of MRI in patients with invasive ductal carcinoma of breast cancer .Methods 75 patients with breast ductal carcinoma treated by surgical treatment were selected . According to the age,75 patients were divided into young group (≤40 years) with 22 cases and elderly group ( >40 years) with 53 cases.The morphology,location,size,border and edge of the two groups were analyzed .The time signal intensity curve ( TIC) was analyzed.Results The proportion of patients with non -luminal invasive ductal carcinoma of the young group was 54.55％,which was higher than 30.19％ of the elderly group,the difference was statistically significant(χ2 =3.94,P=0.047).The proportion of breast cancer infiltrating ductal carcinoma in the young group was 63.64％,which was higher than 37.74％in the elderly group,the difference was statistically signifi-cant(χ2 =4.21,P=0.040).The proportion of the infarcted ductal carcinoma in the young group was 59.09％,and that in the elderly group was 62.26％,the difference was not statistically significant(χ2=2.19,P=0.14).The proportion of breast invasive ductal carcinoma in the young group was 63.64％, which in the elderly group was 54.72％, the difference was not statistically significant (χ2 =0.13,P=0.72).Ⅰ,ⅡandⅢtype of breast ductal carcinoma TIC in the young group were 0cases,14cases,8cases,respectively,which in the elderly group were 0cases,36cases,17cases, respectively,there was no statistically significant difference in TIC grade between the two groups (χ2 =2.26,P=0.13 ) .Conclusion Breast infiltrating ductal carcinoma is mostly pulmonary lump type ,tumor border is unclear;MRI dynamic enhancement technique for the detection of breast invasive ductal carcinoma can reduce misdiagnosis .

[ ABSTRACT] AIM:To investigate the effects of pathological products, urinary proteins and advanced glycosyla-tion end products ( AGE) produced in the progression of chronic kidney disease ( CKD) , on the structure and function of lysosomes in renal tubular epithelial cells ( TECs ) , and try to find a novel approach for preventing or delaying CKD. METHODS:The renal specimens of the untreated patients with minimal change nephrotic syndrome (MCNS), diabetic nephropathy (DN) or normal kidney were collected.The expression of lysosomal-associated membrane protein 1 (LAMP1) and cathepsin B ( CB) was studied in TECs by indirect immunofluorescent staining.Human renal tubular epithelial cell line HK-2 was incubated with 8 g/L urinary proteins or 100 mg/L AGE.The expression of LAMP1 and CB was investigated by indirect immunofluorescence and the activity of CB and cathepsin L ( CL) was measured by biochemical and enzymatic as-says.The degradation of DQ-ovalbumin was also determined.RESULTS: The lysosomal membrane permeabilization oc-curred in the TECs of MCNS and DN patients.After treatment with urinary proteins or AGE-BSA, the lysosomal membrane permeabilization of the HK-2 cells was increased.The activity of CB and CL and degradation of DQ-ovalbumin were de-creased as compared with normal control group.CONCLUSION:The digestive function of lysosome was decreased and ly-sosomal membrane permeabilization occurred in the TECs exposed to urinary proteins and AGE, which might be a key factor to induce the tubulointerstitial fibrosis.

Objective To explore the influence of different blood gas strategies on cerebral protection and blood gas analysis during moderate hypothermic cardiopulmonar.Methods Patients under cardiac valve replacement with extracorporeal circulation (ECC) were performed in this study.The cerebral blood flow (CBF) and regional cerebral oxygen saturation (rSO2) were monitored at 5 points:(1)Induction of anesthesia (T1),(2) after 10 min of the beginning of cardiopulmonary bypass (T2),(3) during the moderate hypothermic phase of CBP managed by the alpha-stat after calibrate blood gas 15 min (T3),(4) pH-stat followed,after calibrate blood gas 15 min (T4),and (5) 10 min after CBP (T5).pH and pCO2 in patients were recorded and analyzed at T3 and T4.Results The CBF of T2 and T3 was lower than that of T1,but the difference was not significant (t =2.841,2.711;P =0.062,0.080).The CBF of T4 and T5 was higher than that of T3,but the difference was not significant (t =1.793,2.135;P =0.119,0.066).The CBF of T5 resumed to before operation.The rSO2 of T2 and T3 was lower than that of T1,but the difference was not significant (t =1.821,2.032;P =0.132,0.267),the rSO2 ofT4 and T5 was higher than that ofT3,but the difference was not significant (t =1.879,2.021;P =0.312,0.075).The rSO2 of T5 resumed to before operation.However,the pH was much lower in pH-stat than alpha-stat (t =17.541,P =0.000) and the pCO2 was much higher than alpha-stat (t =13.914,P =0.000).Conclusions Both pH-stat and alpha-stat have cerebral protection effects.However,compared to pH-stat,alpha-stat could reduce the possibility of acidosis,and maintain the acid-base equilibrium.

Dexmedetomidine and midazolam have been widely used in clinical anesthesia and intensive care unit sedation. These two drugs differ in sedative mechanism. We hypothesized that the neurotoxicity of repeated exposure to dexmedetomidine or midazolam for neonatal mice might be different. Twenty four mice of postnatal day 8 were randomly divided into control (n=8), dexmedetomidine (n=8) and midazolam group (n=8) respectively. In the three groups, saline(10mL/kg), dexmedetomidine(10microg/kg) or midazolam(40mg/kg) was injected intraperitoneally once a day, in the next five days, respectively. Then the brains of the mice in the three qroups were removed and cryosectioned. Apoptotic neural cell in hippocampus region was detected with terminal deoxynucleotydyl transferase -mediated dUTP nick end labeling(TUNEL). Bcl2 and Bax protein expression level in the hippocampus were determined by immunofluorescent staining. In the present study, the number of TUNEL-positive cells from midazolam group ((20 +/-3) /mm2) was larger than that from dexmedetomidine group ((15+/-2) /mm2, P<0. 05) and control group((13+/-3) /mm2, P<0. 05); Bcl-2 protein quantity in hippocampus from control group((790+/-103)/mm2)was significantly lower than that in midazolam group((1187+/- 162)/mm2, P<0.05)and dexmedetomidine group((890+/-125)/mm2, P<0. 05). Bax protein level in control group((942+/-104)/mm2) was also significantly lower than that in midazolam group((1839+/-160)/mm2, P<0. 05)and dexmedetomidine group((1143+/-125)/mm2, P<0. 05); Bax/Bcl-2 ratio in midazolam group(0. 64+/-0. 13) was significantly lower than that in dexmedetomidine group(0. 78 +/-0. 14, P<0. 05) and control group(0. 84+/-0. 15, P<0. 05). Our results suggest that dexmedetomidine has lower neurotoxicity than midazolam for neonatal mice.
Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Dexmedetomidine ; toxicity ; Hippocampus ; drug effects ; pathology ; Mice ; Mice, Inbred C57BL ; Midazolam ; toxicity ; Neurons ; drug effects ; pathology ; Neurotoxicity Syndromes ; etiology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Discrimination of abnormal images from the numerous wireless capsule endoscope (WCE) video sequence images is laborious and time-consuming, so that a computer-based automatic image recognition system is desired for this task. We propose an algorithm to allow feature extraction from each image channel and decision fusion using multiple BP neural networks. The algorithm was tested and the results demonstrated its high efficiency and accuracy in identification of abnormalities in the WCE images.
Algorithms ; Capsule Endoscopy ; methods ; Image Interpretation, Computer-Assisted ; methods ; Pattern Recognition, Automated ; methods