Clinical efficacy of femtosecond laser-assisted cataract surgery combined with PanOptix trifocal intraocular lens implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of femtosecond laser-assisted cataract surgery combined with PanOptix trifocal intraocular lens implantation.METHODS:The retrospective study enrolled 22 cases(26 eyes)of cataract patients who underwent femtosecond laser-assisted cataract surgery combined with PanOptix trifocal intraocular lens implantation from August 2020 to August 2021. Follow-up to 3mo after surgery, the changes of far, intermediate and near visual acuity, aberration, Strehl ratio(SR)and modulation transfer function cutoff(MTF-cutoff)frequency were compared. Defocus curve at 1mo postoperatively was made, and the visual quality and satisfaction were evaluated after 3mo of surgery.RESULTS: The visual acuity of all patients was better than 0.1(LogMAR)at the far, intermediate and near distance at 1d, 1wk, 1 and 3mo postoperatively, and it was significantly improved compared with those before surgery(all P<0.01). The defocus curve transitioned smoothly between +0.5 and -3.0D at 1mo after surgery, and visual acuity was better than 0.63. The total aberration and spherical aberration in the whole eye were significantly lower after surgery than before, and the SR and MTF-cutoff were significantly improved at 1d and 1wk after surgery(all P<0.05). With high satisfaction and good visual quality, patients could watch at far, intermediate and near distance without wearing glasses at 3mo after surgery.CONCLUSION: Femtosecond laser-assisted cataract surgery combined with PanOptix trifocal intraocular lens implantation gave patients a comfortable and satisfactory full-course vision.

Da Chaihutang Inhibits Hepatocellular Carcinoma by Regulating p38 MAPK/IL-6/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveThis study aims to investigate the efficacy and underlying mechanism of Da Chaihutang （DCHT） in treating hepatocellular carcinoma （HCC） in vitro and in vivo. MethodWe employed methyl thiazolyl tetrazolium （MTT） assay and crystal violet staining to observe the proliferation of Hepa1-6 liver cancer cells treated with DCHT at different doses （0， 125， 250， 500， 1 000 mg·L-1） for different time periods （1， 2， 4， 8 days）. The orthotopic liver cancer model was established by injection of 1×106 Hepa1-6 cells into mouse， and then the model mice were randomly assigned into six groups： blank， model， DCHT （0.21， 0.625， 1.875 g·kg-1， ig， qd）， and positive control （5-fluorouracil， 25 mg·kg-1， ip， qod）. After 14 days of administration， the mice were sacrificed， and the liver samples were collected and fixed in 4% paraformaldehyde for hematoxylin-eosin （HE） staining. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Cytoscape 3.7.2， STRING， and DAVID were used for the searching of the key targets of DCHT in treating HCC， the construction of protein-protein interaction （PPI） network， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Quantitative real-time PCR was performed to determine the mRNA level of interleukin-6 （IL-6） in Hepa1-6 cells and liver tissue. Western blotting was employed to measure the protein levels of the proteins involved in the mitogen-activated protein kinase （MAPK） and signal transducers and activators of transcription 3 （STAT3） signaling pathways. ResultDCHT （500， 1 000 mg·L-1） treatment for 4 and 8 days inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner （P<0.05）. The in vivo assay showed that DCHT （high dose， 1.875 g·kg-1） treatment for 14 days led to high differentiation and unobvious heterogeneity of HCC cells and small necrotic area compared with the model group. Network pharmacology analysis predicted that the potential targets of DCHT in the treatment of HCC were mainly the inflammation cytokines such as IL-6， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in HCC microenvironment. The potential signaling pathways involved in the treatment were mainly associated with HCC growth and differentiation， including MAPK and STAT3 signaling pathways. Compared with the blank group， DCHT （1 000 mg·L-1） treatment for 1， 2， 4， and 8 days down-regulated the mRNA level of IL-6 in Hepa1-6 cells （P<0.05）. Similar results were observed in the livers of mice treated with DCHT （0.625， 1.875 g·kg-1）. The in vitro assay demonstrated that DCHT （1 000 mg·L-1） treatment for 4 and 8 days and DCHT （500， 1 000 mg·L-1） treatment inhibited the phosphorylation of extracellular signal-regulated kinases 1/2 （ERK1/2）， c-Jun NH2-terminal kinase/stress-activated protein kinase （JNK）， p38 MAPK， and STAT3 in a dose- and time-dependent manner （P<0.05）. The in vivo assay showed that DCHT （0.625 and 1.875 g·kg-1） treatment only inhibited the phosphorylation of p38 MAPK and STAT3 （P<0.05）. ConclusionThe present study indicates that DCHT can inhibit liver cancer cell proliferation by regulating p38 MAPK/IL-6/STAT3 signaling pathway.

Efficacy of modified folding intraocular lens suspension surgery in treatment of traumatic dislocation of lens / 国际眼科杂志(Guoji Yanke Zazhi)

@# AIM: To evaluate the efficacy of modified folding intraocular lens(IOL)suspension surgery in treatment of traumatic dislocation of lens surgery technique.METHODS: Prospective randomized controlled study. A total of 15 patients underwent the modified folding IOL suspension surgery. Among them, 9 patients chose Akreos AO IOL, and polypropylene sutures were used to thread the haptics of IOL. After guided to puncture out through the sclera, the ends of sutures were thermal expanded and fixed in the sclera. And 6 patients chose Tecnis ZA9003 IOL and no sutures were used. After guided the haptics to puncture out through the sclera, the ends of haptics were thermal expanded and fixed in the sclera. The best corrected visual acuity(BCVA, LogMAR)of all patients and postoperative complication were observed. RESULTS: This study included 15 patients, among them, 7 were male and 8 were female, the mean age was 64.00±9.85 years old, the mean course of diseases was 5.80±3.17 wk. There were no significant differences between the demographic and baseline clinical characteristics. After underwent the modified folding IOL suspension surgery, visual acuity of all patients were obviously improved. After 3mo of the surgery, the BCVA(LogMAR)of patients were improved from 1.28±0.56 to 0.52±0.30. More specifically, the BCVA(LogMAR)of patients who chose Akreos AO IOL were improved from 1.39±0.62 to 0.59±0.25, and those who chose Tecnis ZA9003 IOL of the BCVA(LogMAR)were improved from 1.12±0.45 to 0.42±0.35. Furthermore, there was no severe postoperative complication observed in our study. Only one patient suffered IOL dislocation and the IOL optical surface was mild oblique.CONCLUSION: Modified folding IOL suspension surgery technique resulted in good visual and outcomes with no severe complication, making it an effective option for IOL suspension surgery.

Relationship between postoperative delirium and preoperative modified frailty index in elderly patients undergoing colorectal cancer surgery / 中华麻醉学杂志

Objective:To evaluate the relationship between postoperative delirium and preoperative modified frailty index (mFI) score in elderly patients undergoing colorectal cancer surgery.Methods:The medical records of elderly patients of either sex, aged 65-90 yr, with primary tumor, without radiotherapy and chemotherapy before operation, with the expected operating time ≥ 2 h, undergoing colorectal cancer surgery under general anesthesia, were collected.The patients′ preoperative frailty was assessed using mFI scale.Primary outcome was the incidence of delirium within 7 days after operation, and delirium was assessed using Confusion Assessment Method.The preoperative baseline characteristics, BI score, mFI score and Mini-Mental State Examination were recorded; anesthesia-related information, surgery-related information, intraoperative adverse events, total volume of intraoperative fluid infused, blood loss, and urine output were recorded.The patients were divided into delirium group (D group) and non-delirium group (N group) according to whether delirium occurred or not, and logistic regression analysis was used to screen the risk factors for postoperative delirium in elderly patients with colorectal cancer.Results:A total of 370 patients were enrolled in this study, and the incidence of delirium was 10.8%.There were significant differences in age, ASA grading ratio, mFI score, anesthetic time and total volume of intraoperative fluid infused between group N and group D ( P<0.05). The results of multivariate logistic regression analysis showed that increased age and mFI were independent risk factors for the occurrence of postoperative delirium ( P<0.05). Conclusions:Increased mFI score and age are independent risk factors for postoperative delirium in elderly patients undergoing colorectal cancer.

The role of renal tubular Injury in the transition from acute kidney injury to chronic kidney disease / 医学研究生学报

Acute kidney injury (AKI) is an acute and critical kidney disease that seriously threatens human health and even life. It can lead to the chronic kidney disease (CKD) and end-stage kidney disease (ESRD), causing global public health problems. At present, the transition mechanism from AKI to CKD has not been fully elucidated, and renal tubular injury may play an important role in it. This paper reviews the role of renal tubular injury in the transition from AKI to CKD including cell dedifferentiation, inflammatory cell infiltration, hypoxia and vascular density decline, mitochondrial dysfunction and oxidative stress, G2/M cell cycle arrest, autophagy, TGFβ signaling pathway and Wnt signaling pathway.

Therapeutic effect of massage on denervated skeletal muscle atrophy in rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the therapeutic effects of massage on denervated skeletal muscle atrophy in rats and its mechanism.@*METHODS@#Forty-eight male SD rats were randomly divided into model group (n=24) and massage group (n=24). Gastrocnemius muscle atrophy model was established by transecting the right tibial nerve of rat. On the second day after operation, the gastrocnemius muscle of the rats in the massage group was given manual intervention and the model group was not intervened. Six rats were sacrificed at the four time points of 0 d, 7 d, 14 d and 21 d. The gastrocnemius of the rats were obtained and measured the wet mass ratio after weighing. Cross-sectional area and diameter of the muscle fiber were measured after HE staining. The relative expressions of miR-23a, Akt, MuRF1 and MAFbx mRNA were tested with qPCR.@*RESULTS@#Compared with 0 d, the wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle showed a progressive decline in the model group and massage group. The wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle in the massage group were higher than those in the model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expressions of MuRF1, MAFbx and Akt mRNA were increased first and then were decreased in the model group and massage group. The expression of MuRF1 mRNA in massage group was lower than that in model group on 7 d and 21 d (P＜0.05, P＜0.01). The expression of MAFbx mRNA in massage group was lower than that in model group on 7 d, 14 d and 21 d (P＜0.01, P＜0.05, P＜0.01). The expression of Akt mRNA in massage group was higher than that in model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expression of miR-23a mRNA was increased in the model group and massage group on 21 d, and the expression of miR-23a mRNA in massage group was higher than that in model group (P＜ 0.05).@*CONCLUSION@#Massage can delay the atrophy of denervated skeletal muscle. The mechanism may be related to up-regulation of the expression of miR-23a and Akt mRNA, down-regulation of the expressions of MuRF1 and MAFbx mRNA, inhibition of protein degradation rate, and reduction of skeletal muscle protein degradation.

Research of the effect in intermedin on cell proliferation repair of renal tubular cell hypoxia-reoxygenation injury / 中国药理学通报

Aim To evaluate the effect of intermedin (IMD)on cell proliferation and regeneration in rat tu-bular epithelial cell line (NRK-52E)that was subjec-ted to hypoxia-reoxygenation (H/R)injury.Methods The NRK-52E cells were divided into control group and three model groups (H/R,H/R +primitive vec-tor,H/R +IMD vector).The content of LDH was de-tected to observe the influence of IMD on H/R injury. The cell proliferation was detected by MTT.The cell cycle was detected by flow cytometry.Real-time PCR and western blotting were used to determine mRNA and protein levels.Results ① In comparison to the con-trol,H/R treatment decreased the cell viability and in-creased LDH activity (P <0.01 );in contrast,com-pared to H/R,IMD treatment ameliorated cell viability (79.1 5 ±1 .421 % vs 61 .22 ±1 .63%,P <0.05)and decreased LDH activities by 33.85% (P <0.01 ).②The proliferation of NRK-52E cells was significantly in-hibited by H/R treatment.In comparison to the con-trol,H/R treatment of NRK-52E cells increased the proportion of cells in the G0 /G1 phase but decreased the proportion of cells in the S and G2 /M phases. Moreover,the over-expression of IMD resulted in S and G2 /Mphase redistribution and the accumulation of G2 /M-phase cells.The real-time PCR and western blotting results indicated that the mRNA and protein expression levels of cyclin D1 ,CDK4 and p57 were increased in H/R-treated cells.IMD further stimulated this up-reg-ulated expression of cyclin D1 ,CDK4 and decreased the expression of p57 in NRK-52E cells.④Cyclin D1 had a predominantly nuclear localization in NRK-52Ecells,although cytoplasmic localization was also ob-served.Conclusion The study shows that the over-expression of IMD may promote renal cell proliferation and regeneration after renal tubular cell H/R injury via the up-regulation of cyclin D1 ,CDK and the down-reg-ulation of p57.

Analysis of the lymphocyte subsets in cerebrospinal fluid in patients with HIV infection / 国际检验医学杂志

Objective To explore the lymphcyte subsets distribution in cerebrospinal fluid in patients with HIV infection ,and to investigate the clinical significance of the lymphocyte subsets in cerebrospinal fluid in HIV central nervous system complication . Methods 34 patients with HIV infection ,including 20 patients without nervous system symptoms (simple HIV group) and 14 pa‐tients with nervous system symptoms (neurological HIV group) ,and 15 cases of healthy people (control group) were selected . Flow cytometry was used to detect lymphocyte subsets ,and immunoturbidimetry was used to detect the level of IgG in cerebrospinal fluid .Results The percentage of CD8+ T cells was higher and percentage of CD4+ T cells was lower in the simple HIV group and neurological HIV group than those in the healthy control ,with statistically significant differences (P0 .05) .There were also no significant differece between the sim‐ple HIV group and neurological HIV group in the ratio of each lymphcyte subset in cerebrospinal fluid (P>0 .05) .Conclusion The immune disorder in cerebrospinal fluid in patients with HIV infection may appear in the early time before the nervous system com‐plication .The changing trends of lymphocyte subsets are consistent with the peripheral blood ,which demonstrate that the T lym‐phocyte subsets may be correlated with the nervous system symptoms of HIV .

Progress in the study of targeted drug delivery systems for cancer stem cells / 药学学报

The discovery, sorting and identification methods as well as targeted drug delivery systems for cancer stem cells (CSCs) have been reviewed by consulting the recent research papers. CSCs have been believed to be responsible for the occurrence and development of chemo-resistance, leading to the failure of chemotherapy. Much progress has been made in the approaches for CSCs targeting drug delivery systems. The understanding and targeted drug delivery systems for CSCs are promising to provide an alternative for cancer therapy.

A novel rabbit disc degeneration model induced by fibronectin fragment / 中华外科杂志

<p><b>OBJECTIVE</b>To establish a novel and useful rabbit model of lumbar disc degeneration using microinjection of fibronectin fragment (Fn-f).</p><p><b>METHODS</b>Thirty-two New Zealand white rabbits underwent injection of N-terminal 30 kDa Fn-f (experimental group) or phosphate buffered saline (PBS) (control group) into the central region of L1-2, L2-3, L3-4, L4-5 discs using a 32-gauge microsyringe. Two rabbits (blank group) with no treatments were sacrificed to examine the proteoglycan synthesis of neucleus pulposus (NP) using (35)S-sulfate incorporation assay. At the 4-, 8-, 12-, and 16-week time points, the discs were examined histologically, radiographically, and with proteoglycan synthesis.</p><p><b>RESULTS</b>Histology demonstrated a progressive loss of the cell numbers in NP and architecture destruction in NP and anulus fibrosus (AF) in Fn-f-injected discs over the 16-week study period. The NP regions in Fn-f-injected discs shrinked distinctly after the 4-week time point, and were not discernible with the inner AF by the 16-week time point. Protoglycan synthesis in Fn-f-injected discs decreased progressively (F = 263.241, P = 0.000). At each time point, the Fn-f-injected discs showed significantly decreased proteoglycan synthesis compared with controls (t = -27.010 - -2.833, P < 0.05). The DHI% of the Fn-f-injected discs at the 4-, 8-, 12-, and 16-week time points were 96.5% ± 1.7%, 85.6% ± 3.8%, 77.2% ± 3.5% and 65.5% ± 5.6%, respectively. Comparing with the DHI% of PBS-injected discs (97.4% ± 1.2%), the Fn-f-injected discs exihibited no significant differences in disc heights at the 4-week time point (P > 0.05), but significant decreases in disc heights at the 8-, 12-, and 16-week time points (t = -21.225 - -10.795, P < 0.01). Apparent anterior osteophytes formed at the 12-week time point and enlarged remarkablely by the 16-week time point in the experimental spines.</p><p><b>CONCLUSIONS</b>Fn-f can induce a progressively degenerative process in rabbit discs which is ethical, cost-effective, reproducible, and consistent with the spontaneous degeneration in human. And it seem to be a novel and useful model for the study of disc degeneration at the molecular level.</p>

Effect of adrenomedullin on rat renal tubular epithelial cell apoptosis induced by hypoxia-reoxygenation and its mechanism / 中华肾脏病杂志

Objective To investigate the effect of adrenomedullin on rat renal tubular epithelial cell line (NRK-52E) apoptosis induced by hypoxia-reoxygenation (HR) injury and its mechanism.Methods NRK-52E cells were cultured and randomly allotted to the following 4 groups:control group,HR group,empty plasmid + HR group,ADM + HR group.NRK-52E cells were transfected with pcDNA3.1-myc-his B empty vector or pcDNA3.1-ADM by transfection complex comprising optimal proportion of plasmid and Fugene HD reagents.Cells were counted by trypanblau and cell survival rate was computed.The concentration of lactate dehydrogenase (LDH) was detected by spectrophotometric method to evaluate cell vitality.The apoptotic rate of NRK-52E cells was measured by flow cytometry.The transfer efficiency was detected by immunocytochemistry.The mRNA expressions of ADM,Bax,Bcl-2 and Fas were determined by Semi-quantitative RT-PCR,and active caspase-3,8,9 protein expression were examined by Western blotting.Results Compared with control group,the expression of ADM significantly increased in HR group (P ＜ 0.05).The expression of ADM significantly increased in ADM + HR group than that in empty plasmid + HR group.Compared with control group,in HR group,the living cell counts and cell survival rate significantly decreased; the LDH concentration in media,apoptotic rate and the levels of Bax,Bcl-2,Bax/Bcl-2,Fas,active Caspase -3,8,9 significantly increased (all P ＜ 0.05).Compared with HR group,in ADM + HR group,the living cell counts and cell survival rate significantly increased; the LDH concentration in media,the cell apoptotic rate and the levels of Bax,Bax/Bcl-2,Fas,active Caspase-3,8,9 significantly decreased,while Bcl-2 was promoted (all P ＜ 0.05).The above indexes had no differences between empty plasmid + HR group and HR group (all P ＞ 0.05).Conclusion The increased expression of ADM can inhibit NRK-52E apoptosis induced by HR,and the mechanism might be achieved by inhibiting mitochondrial and death receptor-mediated apoptotic pathways.

Protective mechanism of NALP3-siRNA on rat renal tubular epithelial cells from hypoxia/reoxygenation injury / 中华肾脏病杂志

Objective To explore the mechanism of protecting cells from hypoxia/ reoxygenation (H/R) injury by constructing specific small interference RNA (siRNA) to inhibit NALP3 expression in rat renal tubular epithelial cells (NRK-52E).Methods (1) To establish the H/R injury model of NRK-52E by regulating the pressure of N2 in incubator to hypoxia condition,the cells were cultured with hypoxia for 1 h and then with reoxygenation for 1 h,2 h,4 h,8 h,16 h and 24 h.The activity of lactae dehydrogenase (LDH) in the culture medium,cell count and cell viability,the expression of NALP3 were determined by biochemical method,trypan blue exclusion and Western blotting.(2) The siRNA was transfected into NRK-52E.The irrespective siRNA transfected group wasused as control.NALP3 expression was examined by Western blotting.(3) The cells were divided into 4 groups:control group,H/R group,irrespective siRNA transfected group and NALP3-siRNA transfected group.To establish the H/R injury model of NRK-52E by regulating the pressure of N2 in incubator to hypoxia condition,the cells were cultured with hypoxia for 1 h and then with reoxygenation for 4 h.And the expression of NALP3 was determined by Western blotting.(4)Cellular apoptosis was examined by Annexin V/PI staining and flow cytometry.NF-κB DNA binding activity,IκB-α,Bcl-2 and Bax expression were examined by EMSA and Western blotting.Results (1)Compared with the control group,the activity of LDH significantly increased,cell count and cell viability significantly decreased (all P＜0.05).The expression of NALP3 significantly increased and peaked at 4 h after H/R.(2)The specific siRNA could efficiently inhibit NALP3 expression in NRK-52E.Compared with the irrespective siRNA transfected group,the protein expression of NALP3 was significantly down-regulated in NALP3 siRNA transfected group (P＜0.05).(3)After hypoxia 1 h and reoxygenation 4 h,the activity of LDH and the expression of NALP3 increased.Compared with the irrespective siRNA transfected group,LDH concentration in media and the expression of NALP3 significantly decreased in NALP3-siRNA transfected group.(4)After hypoxia 1 h and reoxygenation 4 h,NF-κB DNA binding activity was increased,IκB-α phosphorylation and degradation,Bcl-2 and Bax were significantly up-regulated.However,compared with the irrespective siRNA transfected group,NF -κB DNA binding activity,IκB-α degradation and Bax/Bcl-2 were significantly decreased (P＜0.05) in NALP3-siRNA transfected group.At the same time,the ratio of apoptosis was significantly increased in three groups than that in control.Compared with the irrespective siRNA transfected group,the ratio of apoptosis in NALP3-siRNA transfected group was significantly decreased (P＜0.05).Conclusions H/R induces the expression of NALP3 in NRK-52E.The synthesized siRNA can inhibit the expression of NALP3 and protect NRK-52E from hypoxia/reoxygenation injury.The mechanism may be via inhibiting the activation of NF-κB,modulating expression of Bcl-2 and Bax,as well as decreasing cell apoptosis.

Up-regulation of intermedin protects kidney from ischemia/reperfuston injury / 中华肾脏病杂志

Objective To investigate the effect of intermedin (IMD) on renal ischemia/ reperfusion (I/R) injury after the up-regulation of IMD. Methods A total of 24 healthy Wistar male rats were randomly divided into four groups,sham-operated group,I/R group,IMD gene transfection +I/R group and empty plamid +I/R group.All the animals were killed at the end of 24 h of reperfusion.Histological changes and renal function were estimated.The expression and site of IMD were determined by Immunohistochemistry method,semi-quantitative RT-PCR and Western blotting.The protein expressions of endothelin 1 (ET-1),tumor necrosis factor αt (TNF-α) were detected by Western blotting. Results Compared with sham-operated group,tubulointerstitial pathological injury was significant aggravated in I/R group (7.6±2.3) and empty plamid +I/R group (7.0±1.8),and such injury was improved in IMD+I/R group (1.5±0.8) (P＜0.05).Compared with I/R group and empty plamid +I/R group,the renal dysfunction of IMD +I/R group was obviously lessened [BUN:(7.73±1.03) mmol/L vs (10.13±2.14) mmol/L,(9.77±1.92) mmol/L; Scr:(58.50±3.27) μmol/L vs (80.33±7.15) μmol/L, (75.67±7.58) μmol/L,all P＜0.05].IMD expression was weak in the plasma of tubulointerstitial cells in sham-operated group,and was up-regulated in I/R group. Compared with I/R group, immunohistochemical IMD expression increased obviously (262.03±67.89 vs 175.57±48.06,P＜0.01).The mRNA expression of IMD in IMD+I/R group was up-regulated significantly by 60.7％,66.1％ and the protein expression of IMD in IMD+I/R group increased significantly by 51.4％,55.9％ as compared to I/R and empty plasmid +I/R group.Meanwhile,the protein expressions of ET-1 and TNF-αt in IMD+I/R group were obviously lower compared with those in I/R group (ET-1:0.08±0.02 vs 0.17±0.02; TNF-α:0.21±0.04 vs 0.35± 0.02,all P＜0.05). Conclusion IMD gene transfected into kidneys of rats prior to I/R surgery can attenuate the over-expressions of both ET-1 and TNF-o in I/R injured rat kidneys as well as the damages to the structure and function of the kidneys.

Effects of intermedin on nitric oxide synthetases in renal ischemia/reperfusion of rats / 中华器官移植杂志

Objective To observe the effects of intermedin (IMD) on nitric oxide synthetase (NOS) in renal ischemia-reperfusion (IR) rat models and the action mechanism.Methods A total of 24 rats were divided into four groups (n =6 each).Group Ⅰ underwent right nephrectomy one week prior to the exposure of left renal pedicles,but did uot receive any I/R.Group Ⅱ underwent right nephrectomy one week prior to left renal I/R surgery.Group Ⅲ underwent right nephrectomy and left renal IMD-pCDNA3.1 ( + ) transfection by ultrasound-mircobubbles and renal I/R surgeries were performed one week after gene transfection.Group Ⅳ was treated with the same way as group Ⅲ except that empty control vector was transfected.All the animals were killed at the end of 24 h of reperfusion.The expression and site of IMD were determined by using immunohistochemistry.Serum levels of BUN and creatinine were determined.The kidney formaldehyde-fixed and paraffin-embedded sections were stained with HE and PAS by standard methods and then histological changes were analyzed semiquantitatively.The mRNA expression levels of endothelial NOS (eNOS),inducible NOS (iNOS) and neuronal NOS (nNOS) in the kidneys of the four groups were detected by using RT-PCR.The protein expression levels of the three NOS mentioned above in the kidneys were semiquantitatively analyzed by Western blotting.Results IMD was weakly expressed in the plasma of tubulointerstitial cells in sham-operated group; whereas IMD expression in the kidneys subject to I/R was increased.Moreover,as compared with I/R group,IMD expression levels were obviously increased (P＜0.01 ).The degree of morphological changes as well as renal dysfunction in group Ⅲ was obviously lessened as compared with group Ⅱ.The mRNA and protein expression levels of eNOS in group Ⅲ were notably increased as compared with group Ⅱ,while the mRNA and protein expression levels of iNOSin group Ⅲ were obviously reduced as compared with I/R group not transfeeted with IMD (P＜0.05).Meanwhile,there were no significant differences in the mRNA and protein expression levels of nNOS among groups Ⅱ,Ⅲ and Ⅳ.Conclusion IMD gene in the kidneys of rats can promote the expression of eNOS and attenuate over-expression of iNOS in the kidneys following I/R,thus protecting against tubulointerstitial damages and renal dysfunction in rat I/R models.

Efficacy research of immune inhibitors sequential therapy according to the cell cycle for the adriamYcin-induced nephropathy rats / 中华肾脏病杂志

Objective To assess the efficacy of different sequential therapy regimens according to the theory of cell cycle on adriamycin-induced nephropathy (AIN) rats. Methods SD rats were randomly divided into five groups:control group (n=8),AIN model group (n=8),MP+ CsA+MMF group (n=8),MP+CsA+CTX treated group (n=8) and MP+FK506+Rapa group (n=8).The levels of 24-hour urinary protein,serum total protein (TP),albumin (Alb),cholesterin (Chol),triglyeride (TG),serum urea nitrogen (BUN),serum creatinine (Scr) were measured.The renal pathological changes were observed by light microscope.The expressions of nephrin and podocin were analyzed by immunohistochemistry and real-time PCR.The expression of CTGF was detected by Western blotting. Results (1)Compared with control group,the levels of 24-hour urinary protein in AIN model group were obviously increased at 2nd,4th,8th and 12th week (all P＜0.01).The level of 24-hour urinary protein were obviously decreased in treatment groups at 8th and 12th week than those in AIN model group (all P＜0.05). (2)The levels of TP and Alb were significantly lower in AIN model group than those in control group (all P＜0.01),and the levels of TG and Chol were significantly higher in AIN model group than that in control group (all P＜0.01).The levels of TP and Alb were significantly higher and the levels of TG and Chol were significantly lower in treatment groups than those in AIN model group (all P ＜0.05). (3)The results of immunohistochemistry indicated the expressions of nephrin and podocin in treatment group rats were obviously higher than those in AIN model group (all P＜0.01). (4)The results of Western blotting indicated the expression of CTGF in treatment group rats was higher than that in AIN model group (P＜0.05).The effect of inhibitting fibrous degeneration in MP +FK506 +Rapa group was more greater than other treatment groups. Conclusions Sequential combined regimens according to the cell cycle can improve the pathological change in adriamycin-induced nephropathy rats,reduce the urine protein,increase the levels of TP and Alb,decrease the levels of TG and Chol,increase the expression of nephrin and podocin,and ameliorate kidney fibrosis.

Effects of decline in renal function with age on the outcome of asymptomatic carotid plaque in healthy adults: a 5-year follow-up study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been long suggested that abnormal clinical factors in the body, such as dyslipidemia and diabetes, can affect the presence of atherosclerosis. However, few studies on the effect of factors within the normal range, such as the loss of renal function with age, on the prevalence of atherosclerosis are few know in healthy individuals. The aim of this study was to investigate risk factors affecting the presence of asymptomatic carotid plaques in a middle-aged and elderly healthy population.</p><p><b>METHODS</b>In this regard, we prospectively evaluated 245 healthy individuals (98 males and 147 females) at baseline and after 5 years. Changes in the presence of carotid plaque between 2003 and 2008 were categorized into four groups, i.e. subjects without plaque at entry (n = 165): Group 1 (without plaque on two occasions, n = 129) and Group 2 (with nascent plaque at follow-up, n = 36); subjects with plaque at entry (n = 80); Group 3 (with plaque regression at follow-up, n = 29) and Group 4 (with plaque on two occasions, n = 51).</p><p><b>RESULTS</b>Univariate analysis showed that the positive rate of carotid plaques in males was higher than that in females at the baseline, and that a significantly inverse correlation existed between the prevalence rate of plaque and aging. Logistic regression analysis of cross-sectional research showed that independent risk factors for the prevalence of atherosclerosis were male gender, lower estimated glomerular filtration rate (eGFR) and higher low-density lipoprotein cholesterol (LDL-C) at the baseline, and older age and lower eGFR were involved in the presence of carotid plaques at follow-up point. However, logistic regression analysis of the longitudinal data showed that older age, decreased eGFR and increased systolic blood pressure (SBP) independently predicted the presence of carotid plaques after 5 years in subjects without plaque at entry. In addition, in subjects with plaque at entry, age, changes in eGFR and the baseline levels of serum albumin (ALB) and serum total bilirubin (BIL) dependently influenced the outcome of carotid plaque.</p><p><b>CONCLUSION</b>Physiological decline of renal function, together with advancing age, was an independent risk factor which consistently affected the presence of carotid atherosclerosis in two categories of healthy individuals.</p>

Intermedin ameliorates renal injury by inhibition of tubular epithelial cell apoptosis in a renal ischemia/reperfusion rat model / 中华肾脏病杂志

Objective To investigate the effect of intermedin (IMD) on tubular cells apoptosis induced by renal ischemia/reperfusion (I/R) injury and its associated mechanism.Methods A total of twenty-four male Wistar rats were randomly divided into four groups (control group, I/R group, empty plasmid group and IMD group). One week after the removal of right kidney, ultrasound plasmid was used to transfect empty or IMD plasmid into the left kidney. Renal I/R model was made by clasping the left renal artery for 45 minutes. Tubular cell apoptosis was determined by TUNEL. Expression of Bax, Bcl-2, Fas was detected by semi-quantitative RT-PCR.Activity of caspase-8 and caspase-9 was evaluated with commercially available kits respectively.Protein level of caspase-3 was measured by Western blotting analysis. Results Compared with control group, apoptosis of tubular epithelial cells, expression of Bax and Fas, activities of caspase-8 and caspase-9, as well as protein level of caspase-3 were all significantly increased in I/R group (all P＜0.05). IMD pre-treatment significantly inhibited all these effects (all P＜0.05). There were no differences of above parameters between empty plasmid group and I/R group. Conclusion IMD pre-treatment protects against renal I/R injury by inhibion of tubular epithelial cell apoptosis.

Effect of intermedin on the expressions of angiogenesis-related genes induced by renal ischemia reperfusion injury / 中华肾脏病杂志

Objective To investigate the effect of intermedin (IMD) on the expressions of angiogenesis-related genes induced by renal ischemia reperfusion injury (IRI).Methods Wistar rats were randomly divided into four groups: control group,IRI group,empty plasmid group and IMD plasmid group.One week after removing the right kidney,eukaryotic expression vector encoding rat IMD gene was transfected into the left kidney using an ultrasound-microbubble mediated system.Renal IRI model was induced by clamping left renal arteries for 45 minutes followed by reperfusion for 1 d,2 d,3 d,4 d,7 d and 14 d.The expressions of hypoxia inducible factor-1α (HIF-1o),vascular endothelial growth factor (VEGF) and angiopoietin receptor Tie-2 were examined by RT-PCR and Western boltting.Results Compared with control group,an increase in HIF-1α,VEGF and Tie-2 was observed in the IRI group at d 1,d 2 and d 3 (allP＜0.05).The expression of HIF-1o peaked at d 1 d(P＜0.05),while VEGF and Tie-2 at d 2 (P＜0.05),followed by a decrease that was similar to the control levels at d 4(P＞0.05).Compared with the IRI group,the expressions of HIF-1α,VEGF and Tie-2 of IMD group were much higher and all reached the peak at d 1 (P＜0.05),maintained at d 2-4 (P＜0.05),followed by a decrease at d 7(P＞0.05).The above indexes had no differences between empty plasmid group and IRI group(P＞0.05).Conclusions IMD pretreatment may play an important role in the process of repair and regeneration after renal ischemia reperfusion injury byimproving the expressions of angiogenesis-related genes(HIF-1α,VEGF and Tie-2) induced by renal ischemia reperfusion injury.

Effect of intermedin pretreatment on repair and regeneration process of renal ischemia reperfusion injury / 中华肾脏病杂志

ObjectiveTo explore the effect of intermedin pretreatment on repair and regeneration process of renal ischemia reperfusion (IR) injury.Methods Male Wistar rats were randomly divided into four groups: sham group,IR group,empty plasmid group and IMD group.One week after removing the right kidney,eukaryotic expression vector encoding rat IMD gene was transfected into the left kidney using an ultrasound-microbubble-mediated system,and transfection effect was detected by Western blotting and RT-PCR.After successful transfection,renal IR injury model was induced by clamping left renal arteries for 45 minutes followed by reperfusion.BUN and Scr were tested.Renal pathology was observed by PAS and HE staining.The proliferation of tubular epithelial cells was detected by SABC immunohistochemical method.Results (1)The expression of IMD protein and mRNA in IMD group was significantly up-regulated compared to empty plasmid group(P＜0.05),reaching the peak at day 7,and the difference was not significant with that at day 4.(2)Compared with sham group,BUN and Scr were obviously increased at day 1and 2 in IR group(P＜0.05).However,compared with IR group,BUN and Scr in IMD group decreased obviously(P＜0.05).Differences between IR group and empty plasmid group were not significant(P＞0.05).(3)Kidney tubules in IR group,IMD group and empty plasmid group were injuryed,but the injury in IMD group was less serious compared with that in IR group and empty plasmid group.The injury in three groups was the most severe at day 2 after reperfusion.(4)The number of PCNA positive cells evidently increased at day 7 in IR group and empty plasmid group,but the number of PCNA positive cell evidently increased at day 3 in IMD group.Compared with IR group 1 to 4 days after perfusion,PCNA positive cells in IMD group increased obviously (P＜0.05).Compared with IR group day 7,PCNA expression in IMD group 7 d was obviously decreased(P＜ 0.05).Conclusion IMD pretreatment can induce tubular epithelial cells proliferative and accelerate the repair and regeneration progress in IR injury kidneys.

Effects of intermedin pretreatment on associated repairing genes in the kidney of rats with renal ischemia-reperfusion injury / 中华肾脏病杂志

Objective To investigate the effects of intermedin (IMD) pretreatment on associated repairing genes of the rats with injured kidneys by ischemia reperfusion injury (IRI)during the repair and regeneration process.Methods A total of 144 healthy male Wistar rats were randomly divided into 4 gourps:sham opration group,IRI group,empty plasmid group (EP)and IMD group.After resection of right kidneys of the rats,plasmid was transfected into the left kidneys by using ultrasonic microbubble technology.After one week,the renal IRI models were programmed.The samples of renal tissues after 1 d,2 d,3 d,4 d,7 d and 14 d of reperfusion were harvested respectively,then the mRNA expressions of the Pax-2,ZO-1,Ncam,Wt-1 and vimentin in renal tissues were detected by RT-PCR; the protein expressions of Pax-2,Wt-1 and vimentin were analyzed by Western blotting and the protein expressions of ZO-1 and Ncam were measured by ELISIA.Results (1) Compared with the sham group,the mRNA and protein expression of Pax-2,ZO-1,Ncam,Wt-1 and vimentin of the rats in IRI group increased significantly from day 1 to day 3 (P＜0.05),which peaked at day 2.After day 4,the above expressions in IRI group returned to normal level.(2) In IMD group,the mRNA and protein expressions of Pax-2,Zo-1,Ncam,Wt-1 and vimentin were significantly higher than those in other 3 groups (P＜0.05) at the same time after IRI day 1 to day 4,with a maximum in day 2.(3) The above expressions in IRI group,EP group,IMD group had no significant differences compared with sham group after day 7 or day 14 respectively (P＞0.05),and either between IRI group and EP group,though the expressions of the genes in IRI group and EP group increased compared with sham group after day 4.(4) The above expressions between IRI group and EP group also had no significant difference (P＞0.05).(5) Changes of ZO-1 and Ncam protein expression detected by ELISA were similar to those abore mRNA and protein expression by RT-PCR and Western blotting.Conclusion IMD pretreatment plays an important role in up-regulation of the expressions of associated repair genes during the process of repair and regeneration after renal ischemia reperfusion injury.