AIM:To investigate the possible mechanism how orphan nuclear receptor 4A1(NR4A1)affects renal fibrosis in unilateral ureteral obstruction(UUO)mice.METHODS:(1)Specific pathogen-free(SPF)male C57BL/6J mice(5 to 6 weeks old)were randomly divided into sh-Con+sham group(n=6),sham+sh-NR4A1 group(n=6),sh-NR4A1+UUO group(n=6),and sh-NR4A1+UUO group(n=6).Renal NR4A1 knockdown mice were prepared by intrarenal injection of NR4A1 viral vector.(2)SPF male C57BL/6J mice(5 to 6 weeks old)were randomly assigned to in sham group,UUO group,and UUO+cytosporone-B(Csn-B)group.An animal model of renal fibrosis was prepared by UUO,and Csn-B was intervened for 14 days.HE,Masson,and Sirius red staining were used to observe renal pathological damage.Immunohistochemistry and Western blot were performed to detect the expression of NR4A1,interferon-γ(IFN-γ),α-smooth muscle actin(α-SMA)and vimentin.The purpose of this study is to observe the regulatory effect of NR4A1 on UUO-induced renal fibrosis.RESULTS:(1)The expression of NR4A1 was decreased in kidney tissues of UUO mice(P<0.05).(2)HE staining results showed that there are tubular dilation,atrophy,and massive inflammatory cell infiltra-tion in sh-Con+UUO group,and NR4A1 knockdown can aggravate UUO-induced kidney damage(P<0.05).The results of Masson and Sirius red staining showed a banded distribution of collagen deposition in the sh-Con+UUO group,and colla-gen deposition increased significantly after NR4A1 knockdown(P<0.05).Treatment with Csn-B could improve renal path-ological damage and reduce collagen deposition.(3)UUO could upregulate the expression of α-SMA and vimentin,and NR4A1 knockdown could significantly increase UUO-induced their expression(P<0.05).In addition,Csn-B could im-prove UUO-induced renal fibrosis(P<0.05).(4)The expression of IFN-γ was increased in UUO mice,and NR4A1 knockdown could upregulate UUO-induced IFN-γ expression(P<0.05).Moreover,Csn-B could down-regulate UUO-in-duced IFN-γ expression(P<0.05).CONCLUSION:NR4A1 can affect renal fibrosis by regulating IFN-γ in UUO mice.

AIM:This study aims to investigate the impact of chronic kidney disease(CKD)on the growth,development,and cognitive function of offspring rats,and to evaluate the effects of esaxerenone(ESAX)intervention.METHODS:Thirty female non-pregnant Wistar rats were randomly assigned to three groups:sham operation+pregnancy(control group),UUO+pregnancy(model group),and UUO+pregnancy+esaxerenone(treatment group),with 10 rats in each group.CKD was induced in the UUO+pregnancy and UUO+pregnancy+esaxerenone groups by performing uni-lateral ureteral obstruction(UUO),while the sham operation+pregnancy group underwent a non-ligated and non-clipped ureter procedure.Rats in the treatment group received esaxerenone at a dosage of 1 mg·kg-1·d-1.Vaginal smears were per-formed weekly from the 8th week post-UUO to monitor the estrous cycle.Female and male rats in pre-estrus or estrus were paired in a 2∶1 ratio,and the day with the first appearance of sperm in vaginal smears was recorded as the first day of preg-nancy.Offspring were delivered 21 to 22 days post-gestation,and 10 offspring from each group were selected for further experimentation:sham-offspring(sham-offspr)group,UUO-offspro group,and esaxerenone treatment offspring(ESAX-offspr)group.At 21 days of age,offspring weight and tail length were measured.Behavioral tests,including the open field test,Y maze test,and Morris water maze test,assessed learning and memory abilities.Serum levels of aldosterone,5-hydroxytryptamine(5-HT),and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were assessed using conventional biochemical methods.Renal pathology was examined using Hematoxylin-Eosin(HE)staining.RESULTS:Offspring in the UUO-offspr group had reduced body weight and tail length compared to the sham-offspr group(P＜0.05).Behavioral tests indicated that exploration and memo-ry abilities were significantly impaired in the UUO-offspr group compared to the sham-offspr group(P＜0.05),while the ESAX-offspr group showed improved behavioral development compared to the UUO-offspr group(P＜0.05).ELISA results revealed decreased levels of serum 5-HT,BDNF,and aldosterone in the UUO-offspr group compared to the sham-offspr group(P＜0.01),with increased levels in the ESAX-offspr group(P＜0.05).Renal function tests showed elevated SCr and BUN levels in the UUO-offspr group compared to the sham-offspr group(P＜0.01),while levels in the ESAX-offspr group were reduced(P＜0.01).HE staining demonstrated mild tubular dilation and inflammatory cell infiltration in the UUO-offspr group,whereas the ESAX-offspr group had well-arranged tubules with reduced inflammation.CONCLU-SION:Chronic kidney disease adversely affects the growth,development,and cognitive function of offspring rats by 21 days of age.Esaxerenone intervention can mitigate these detrimental effects on growth,development,and cognitive abili-ties in offspring rats.

AIM:To investigate the possible mechanism how orphan nuclear receptor 4A1(NR4A1)affects renal fibrosis in unilateral ureteral obstruction(UUO)mice.METHODS:(1)Specific pathogen-free(SPF)male C57BL/6J mice(5 to 6 weeks old)were randomly divided into sh-Con+sham group(n=6),sham+sh-NR4A1 group(n=6),sh-NR4A1+UUO group(n=6),and sh-NR4A1+UUO group(n=6).Renal NR4A1 knockdown mice were prepared by intrarenal injection of NR4A1 viral vector.(2)SPF male C57BL/6J mice(5 to 6 weeks old)were randomly assigned to in sham group,UUO group,and UUO+cytosporone-B(Csn-B)group.An animal model of renal fibrosis was prepared by UUO,and Csn-B was intervened for 14 days.HE,Masson,and Sirius red staining were used to observe renal pathological damage.Immunohistochemistry and Western blot were performed to detect the expression of NR4A1,interferon-γ(IFN-γ),α-smooth muscle actin(α-SMA)and vimentin.The purpose of this study is to observe the regulatory effect of NR4A1 on UUO-induced renal fibrosis.RESULTS:(1)The expression of NR4A1 was decreased in kidney tissues of UUO mice(P<0.05).(2)HE staining results showed that there are tubular dilation,atrophy,and massive inflammatory cell infiltra-tion in sh-Con+UUO group,and NR4A1 knockdown can aggravate UUO-induced kidney damage(P<0.05).The results of Masson and Sirius red staining showed a banded distribution of collagen deposition in the sh-Con+UUO group,and colla-gen deposition increased significantly after NR4A1 knockdown(P<0.05).Treatment with Csn-B could improve renal path-ological damage and reduce collagen deposition.(3)UUO could upregulate the expression of α-SMA and vimentin,and NR4A1 knockdown could significantly increase UUO-induced their expression(P<0.05).In addition,Csn-B could im-prove UUO-induced renal fibrosis(P<0.05).(4)The expression of IFN-γ was increased in UUO mice,and NR4A1 knockdown could upregulate UUO-induced IFN-γ expression(P<0.05).Moreover,Csn-B could down-regulate UUO-in-duced IFN-γ expression(P<0.05).CONCLUSION:NR4A1 can affect renal fibrosis by regulating IFN-γ in UUO mice.

AIM:This study aims to investigate the impact of chronic kidney disease(CKD)on the growth,development,and cognitive function of offspring rats,and to evaluate the effects of esaxerenone(ESAX)intervention.METHODS:Thirty female non-pregnant Wistar rats were randomly assigned to three groups:sham operation+pregnancy(control group),UUO+pregnancy(model group),and UUO+pregnancy+esaxerenone(treatment group),with 10 rats in each group.CKD was induced in the UUO+pregnancy and UUO+pregnancy+esaxerenone groups by performing uni-lateral ureteral obstruction(UUO),while the sham operation+pregnancy group underwent a non-ligated and non-clipped ureter procedure.Rats in the treatment group received esaxerenone at a dosage of 1 mg·kg-1·d-1.Vaginal smears were per-formed weekly from the 8th week post-UUO to monitor the estrous cycle.Female and male rats in pre-estrus or estrus were paired in a 2∶1 ratio,and the day with the first appearance of sperm in vaginal smears was recorded as the first day of preg-nancy.Offspring were delivered 21 to 22 days post-gestation,and 10 offspring from each group were selected for further experimentation:sham-offspring(sham-offspr)group,UUO-offspro group,and esaxerenone treatment offspring(ESAX-offspr)group.At 21 days of age,offspring weight and tail length were measured.Behavioral tests,including the open field test,Y maze test,and Morris water maze test,assessed learning and memory abilities.Serum levels of aldosterone,5-hydroxytryptamine(5-HT),and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were assessed using conventional biochemical methods.Renal pathology was examined using Hematoxylin-Eosin(HE)staining.RESULTS:Offspring in the UUO-offspr group had reduced body weight and tail length compared to the sham-offspr group(P＜0.05).Behavioral tests indicated that exploration and memo-ry abilities were significantly impaired in the UUO-offspr group compared to the sham-offspr group(P＜0.05),while the ESAX-offspr group showed improved behavioral development compared to the UUO-offspr group(P＜0.05).ELISA results revealed decreased levels of serum 5-HT,BDNF,and aldosterone in the UUO-offspr group compared to the sham-offspr group(P＜0.01),with increased levels in the ESAX-offspr group(P＜0.05).Renal function tests showed elevated SCr and BUN levels in the UUO-offspr group compared to the sham-offspr group(P＜0.01),while levels in the ESAX-offspr group were reduced(P＜0.01).HE staining demonstrated mild tubular dilation and inflammatory cell infiltration in the UUO-offspr group,whereas the ESAX-offspr group had well-arranged tubules with reduced inflammation.CONCLU-SION:Chronic kidney disease adversely affects the growth,development,and cognitive function of offspring rats by 21 days of age.Esaxerenone intervention can mitigate these detrimental effects on growth,development,and cognitive abili-ties in offspring rats.

Objective To explore the characteristics of TCM syndromes in patients with coronary heart disease complicated with hypertension and diabetes based on latent structure model.Methods A multi-center cross-sectional study was used to collect the four diagnostic information of patients with coronary heart disease by using the Four Diagnostic Collection Scales of TCM developed by our research group,and a clinical database was established.Combined with frequency analysis and expert opinions,the four diagnostic information was screened to construct a latent structure model.Results Totally 702 patients with coronary heart disease complicated with hypertension and diabetes were collected.A total of 40 high-frequency four-diagnosis symptoms were screened,and 18 latent variables were obtained by latent structure model analysis.The model BIC score was-17 604.38.The latent variables in the model were comprehensively clustered,and it was found that the syndrome elements of disease location in patients with coronary heart disease complicated with hypertension and diabetes were mainly heart,liver,kidney,etc.,and the syndrome elements of disease nature were mainly qi deficiency,yin deficiency,qi stagnation,phlegm turbidity,blood stasis,etc.The syndrome types were mainly phlegm and blood stasis syndrome,spleen and kidney yang deficiency syndrome,liver depression and qi stagnation syndrome,liver and kidney yin deficiency syndrome,damp-heat intrinsic syndrome,and the mutual information and information coverage between each syndrome type and the four diagnostic information were suggested.Conclusion Latent structure model analysis can provide a qualitative and quantitative basis for the syndrome classification of patients with coronary heart disease complicated with hypertension and diabetes.

AIM:To explore the mechanisms behind the inhibition of lymphangiogenesis in pregnant rats with obstructive nephropathy and assess the protective effects on kidney function.METHODS:Forty nulliparous female Wi-star rats were randomly assigned to four groups:sham operation,sham operation+pregnancy,model,and Esaxerenone groups,with 10 rats in each group.Renal injury was induced in the model and Esaxerenone groups via unilateral ureteral obstruction(UUO).The other two groups underwent ureteral dissociation without ligation.Nine weeks post-UUO,female rats in the sham operation+pregnancy,model,and Esaxerenone groups were mated with male rats(2:1 ratio)to establish a rat model of obstructive nephropathy during pregnancy.Starting the day after UUO,rats in the Esaxerenone group re-ceived Esaxerenone at 1 mg·kg-1·d-1.On the 18th day of pregnancy,24-hour urine was collected using metabolic cages.The following day,the rats were sacrificed,serum samples collected,and the contralateral kidney removed.Blood urea ni-trogen(BUN)was measured using standard biochemical methods,and endogenous creatinine clearance rate(Ccr)was calculated.Kidney tissue pathology was assessed using HE,Masson,and Sirius red staining.Serum aldosterone levels were determined via ELISA.Immunohistochemistry,real-time PCR,and Western blot were employed to assess mineralo-corticoid receptor(MR)activation,lymphangiogenesis,signaling pathways,and fibrosis-related markers.RESULTS:Renal function tests revealed increased BUN levels and decreased Ccr in the model group(P<0.01).Pathological exami-nation showed dilated renal tubules,significant collagen deposition,and inflammatory cell infiltration in the model group.ELISA results indicated a significant increase in serum aldosterone levels in the model group(P<0.01).Immunohisto-chemistry showed enhanced nuclear translocation of MR in the kidneys of the model group post-activation.Western blot and real-time PCR demonstrated a marked increase in neutrophil gelatinase-associated lipocalin(NGAL)expression in the model group(P<0.01).Additionally,the expression of vascular endothelial growth factor C(VEGF-C)and its receptor VEGFR3 was significantly elevated in the renal tubulointerstitium of the model group,as shown by both immunohistochem-istry and real-time PCR(P<0.01).The PI3K/Akt signaling pathway was activated in the model group,with significantly increased phosphorylation levels observed primarily in renal tubular epithelial and interstitial cells(P<0.01).Collagen type III(Col III)expression,primarily in the renal tubulointerstitium,was also significantly upregulated in the model group,consistent with real-time PCR results(P<0.01).Esaxerenone treatment improved renal function,reduced patho-logical damage,inhibited aldosterone secretion,and downregulated the expression of MR,NGAL,VEGF-C,VEGFR3,phosphorylated PI3K,phosphorylated Akt,and Col III(P<0.01).CONCLUSION:Esaxerenone mitigates aldosterone-induced MR activation,modulates the PI3K/Akt signaling pathway,reduces lymphangiogenesis in the contralateral kidney of pregnant rats with obstructive nephropathy,decreases collagen deposition,and delays the progression of renal intersti-tial fibrosis.

BACKGROUND: Poor root canal filling or poor post-core crown restoration can cause microleakage between the implant material and the tooth, leading to secondary infection of the periapical tissue and affecting long-term effect of tooth restoration. OBJECTIVE: To analyze the microleakage in a glucose penetration model when post space preparation is performed with different timing and remaining lengths. METHODS: Eighty-six freshly extracted mandibular premolars from the Orthodontics Department of Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University were randomly divided into eight groups: positive control group (n=10) undertook root canal preparation; negative control group (n=10) undertook root canal preparation and filling but not post space preparation; A1, B1 and C1 groups (n=11 per group) were subjected to root canal filling immediately followed by post space preparation with the filling material of 4 mm, 5 mm, and 6 mm in length, respectively; A2, B2 and C2 groups were subjected to root canal filling and 1 week after filling, the three groups underwent post space preparation with the filling material of 4, 5 and 6 mm in length, respectively. At 48 hours after post space preparation, the integration of root canal wall and filling material was observed by scanning electron microscopy. The glucose microleakage model was used to detect the amount of glucose leaking from the crown to the root in each group. RESULTS AND CONCLUSION: (1) Under the scanning electron microscope, the fillings were most tightly bonded to the root canal wall in C1, while microcracks were most apparent in A2. (2) According to the measurement of glucose penetration model, A2 showed more microleakage than A1 (P < 0.05), B2 showed more microleakage than B1 (P < 0.05), and there was no statistically significant difference between C1 and C2 (P> 0.05). No significant difference was found among A1, B1 and C1 (P> 0.05), B2 showed no statistical difference in the microleakage from A2 and C2 (P> 0.05), but A2 showed more microleakage than C2 (P′ < 0.017). These results indicate that immediate post space preparation is superior to delayed preparation in reducing the microleakage. For immediate post space preparation, the remaining length of the filling material has no effect on the microleakage, but for delayed preparation, the filling material of at least 5 mm in length should be preserved.

Objective: To investigate the physical properties of Ti-6Al-4V clasps generated by selective laser melting (SLM) with different construction directions and to compare these clasps with cast clasps, which could provide a basis for fabricating SLM clasps with high precision and excellent mechanical properties. Methods: Ti-6Al-4V clasps were fabricated by SLM at 0 degrees (SLM0 group), 45 degrees (SLM45 group) and 90 degrees (SLM90 group) (n = 12). Twelve clasps were cast by the casting method as the control group. Meanwhile, four metal abutments were cast randomly as the abutments of the four groups. X-ray was used to detect cracks in the clasps of each group. The roughness of the clasps was measured by confocal microscopy, the fitness tests between clasps and abutment were processed by stereomicroscopy, and the microstructure of clasps in each group was observed under a metallographic microscope to evaluate the physical properties. Results : There were 0-8 visible cracks in the casting group but no obvious defects in the SLM groups. The maximum surface roughness was observed in the cast group (18.102 ± 3.762) μm, while the minimum roughness was observed in the SLM90 group (5.942 ± 1.486) μm (P < 0.05). There was no statistically significant difference in surface roughness between the SLM0 group [(8.711 ± 2.378) μm] and the SLM45 group [(8.513 ± 1.161) μm]. Fitness was worst in the casting group [(68.445 ± 14.876) μm] and best in the SLM90 group [(33.417 ± 5.880) μm] (P < 0.05). There was no statistically significant difference in fitness between the SLM0 group [(52.917 ± 12.102) μm] and the SLM45 group [(50.889 ± 7.011) μm]. In addition, the growth direction of the β grains was roughly parallel to the build direction, and acicular α grains were present between β grains. SLM was composed of fine grains, while the cast group had large grains. Conclusions Specimens generated by SLM had finer grains than cast specimens. In addition, SLM90 clasps had the highest fitness and the lowest surface roughness.

Objective To explore the influence of collateral circulation on the cognition of persons with severe unilateral carotid artery stenosis or occlusion using transcranial Doppler (TCD) imaging combined with P300.Methods A total of 185 patients with stenosis or occlusion of the carotid artery were enrolled and randomly divided into a monocollateral group (n=83),a multicollateral group (n=79) and a noncollateral group (n=23).The monocollateral group was further divided into an anterior communicating artery (AcoA) group,an ophthalmic artery (OA)group and a post communicating artery (PcoA) group according to their collateral circulation.All patients and 40 normal controls (NC) were tested using the Montreal cognitive assessment (MoCA) and P300,and the correlation between the MoCA and P300 scores was analyzed.Results Compared with the NC group,all the other three groups had significantly lower average MoCA scores and P300 amplitudes.They also had significantly longer average P300 latency periods.Compared with the multicollateral group,both the monocollateral and noncollateral groups had significantly lower average MoCA scores and P300 amplitudes and longer P300 latencies.Comparing the monocollateral group with the noncoilateral group revealed the same trends.Among the monocollateral patients the average MoCA score of the AcoA group was significantly higher than the PcoA and OA group averages,while their average P300 latency period was significantly shorter and the amplitude significantly greater than the PcoA group's average.Correlation analyses showed that the MoCA score was negatively correlated with the P300 latency,but positively correlated with the P300 amplitude.Conclusions Collateral circulation can protect the cognitive function of patients with unilateral stenosis or occlusion of the internal carotid artery to some extent,with multicollateral circulation being more effective than monocollateral and AcoA circulation superior to both PcoA and OA circulation.The MoCA score is significantly correlated with the latency period of P300 in such cases.

Objective : To investigate the clinical efficacy of prosthesis retained by metal clasp and flexible clasp in the repair of type Ⅴ maxillary defects after tumor resection. Methods: 23 maxillary tumor surgical patients were selected in this study and restored with maxillofacial prosthesis. Total 24 prosthesis combined with metal clasp and flexible dentures were followed up for half a year to 2 years. Results : After the application of prosthesis, better maxillofacial appearances are presented in all of the patients, Watian drinking water tests are improved to grade Ⅰ or Ⅱ from grade Ⅳ or Ⅴ in 21 patients, there was significant difference (P < 0.05); Soft diet can be masticated on affected side in 15 patients; The mean speech intelligibility score with and without prosthesis were (83.2 ± 7.3)% and (36.6 ± 5.6)%, there was significant difference (P < 0.05); Favorable hygienic situations of oral cavity and prosthesis are maintained in 18 patients. Conclusion Prosthesis combined with metal clasp and flexible denture performed favorable clinical efficacy and contributed to improve the living quality and mental health after tumor resection.