Objective To investigate the mechanism of the pathogenesis of diabetic nephropathy (DN) by detecting the expressions of transforming growth factor (TGF)-β, Smad proteins andα-smooth muscle actin (α-SMA) in kidney biopsy of patients with diabetic nephropathy (DN). Methods Twenty-eight patients with DN who underwent renal biopsy were col-lected as DN group. Ten subjects without DN who underwent nephrectomy were taken as control group. The expressions of TGF-β1, TGF-βRⅠ,TGF-βRⅡ,Smad2/3 andα-SMA in renal tissues were detected by immunohistochemistry stain. Results (1)TGF-β1,TGF-β RⅠ,TGF-β RⅡ,and Smad2/3 were expressed in the glomeruli and tubules of both DN group and control group, while the expressions of TGF-βand Smad proteins were significantly higher in DN group than those in control group. At the early stage of DN, TGF-βand Smad proteins were significantly expressed even though there was no remarkable lesions observed by light microscopy. There was no correlation between increased expression and the progres-sion of DN. These proteins were not expressed after glomerulus and renal tubule fibrosis. (2) In control group,α-SMA was identified only in the vascular walls, glomerulus and renal tubules, while it was expressed in almost all parts of kidney in DN group. Conclusion TGF-β and Smad signals involved in the pathogenesis of DN, which may have similar pathogenesis with immune complex glomerulonephritis.

AIM:We generated transgenic mice of NKCC1-/-(homozygous mutant),NKCC1+/-(heterozygous)and NKCC1+/+(wild-type)that have a targeted disruption in the NKCC1 gene to investigate the role of Na-K-2Cl(NKCC1)channel in auditory function of the inner ear.METHODS:Hearing threshold and endocochlear potential(EP)were measured in the NKCC1-/-,NKCC1+/-and NKCC1+/+ mice by auditory brainstem response(ABR)and EP recordings,respectively.The inner ears of the mice were removed and examined morphologically with the light microscope.RESULTS:The auditory function of NKCC1+/+ mice was normal,the mean value for ABR thresholds in response to click sound was [(23.13?3.78)dB,SPL],EP was(98?16)mV.The mean value for ABR thresholds to click sound was elevated in NKCC1+/-mice [(38.49?12.29)dB,SPL],relative to that significantly increased in NKCC1+/+ mice(P

Objective:To investigate the effect of miR-106a on osteoarthritis.Methods:Twenty-four S-D female rats were randomly divided into three groupsaccording to the random number table: the sham operation group, the osteoarthritis (OA) group and the miR-106a mimic group. Eightweeks after operation, all rats were killed and articular cartilage was separated from the medial tibial plateau of each rat. Histopathology was used to observe the morphological changes and denatured quantity of chondrocytes, the level of inflamm-atory cytokines [interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-β 1], the expression of apoptosis receptor p65, DR6 protein and the expression of mir-106a RNA. The mean between groups was compared by one-way analysis of variance (ANOVA), and the least significant difference (LSD)- t test was used for the comparison between the two groups. Results:Histopathological staining results showed that the articular surface and synovium of rats in the sham operation group were intact, the chondrocytes were arranged horizontally, and the articular cartilage edge was smooth.In the OA group, the articular cartilage edge was seriously damaged and the arrangement of chondrocytes was disordered.In the miR-106a simulation group, the cartilage structure tended to be normal, occasionally uneven, and the articular cartilage surface was not smooth. Compared with sham operation group, the expression of miR-106a in OA group was significantly decreased ( F=918.02, P<0.01); the expression of inflammatory mediators (IL-1, IL-6, TNF-β) in OA group was also signifi-cantly increased ( F=41 914.86, P<0.01; F=64 85.16, P<0.01; F=8 873.31, P<0.01). The expression levels of DR6 and p65 in OA group were higher ( F=2 319.338, P<0.01; F=1 253.882, P<0.01). Compared with OA group, the levels of inflammatory mediators (IL-1, IL-6, TNF-β) in miR-106a mimetic group were significantly decreased (1.270±0.020, 6.040±0.170, 5.690±0.080), and the expressions of DR6 and p65 were decreased (1.53±0.09, 0.41±0.04). Conclusion:miR-106a can reduce the inflammatory changes and the degeneration of chondrocytes in osteoarthritis rats.

Objective: To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke. Methods: Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI. Results: A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke. Conclusion Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.

OBJECTIVETo investigate the changes of vasoconstriction and vasodilatation under different temperature conditions and the protective effects of Vitamin E (Vit E) against endothelial injury induced by hypothermia.

METHODSThe tail arterial rings were prepared for isometric tension recording using multi wire myograph system. The effect of temperature on relaxation and construction was evaluated. Incubate the arterial rings with different concentration of Vit E when they were exposed to hypothermia, then acetylcholine (ACh)-induced endothelium-dependent relaxation was investigated to evaluate the activity of endothelial.

RESULTS(1) The hypothermia could enhanced the dose-dependent construction induced by PE in mice tail artery. (2) Exposure to hypothermia also resulted in increase of sodium nitroprusside (SNP)-induced re-After incubation with Vit E, the vascular relaxation responses to ACh increased in an endothelium-dependent manner, when compared with the hypothermia-treated group.

CONCLUSIONThe vascular function of constriction was attenuated by hypothermia, while the relaxation was increased. Vit E could prevent the hypothermia-induced decrease in vascular endothelial cells.

Animals ; Arteries ; drug effects ; physiology ; Cold Temperature ; Hypothermia ; In Vitro Techniques ; Male ; Mice ; Prazosin ; pharmacology ; Solanaceous Alkaloids ; pharmacology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology ; Vitamin E ; pharmacology

Background Porcine fibrin sealant kit has been widely used in surgery for clotting and woundssealing.It is thought to be a substitution for inert gas and silicone oil in vitrectomy.But whether it produce toxic effect on retina or not after intravitreal injection is still studying.Objective This study aimed to investigate the retinal toxicity of porcine fibrin sealant kit following intraocular application.Methods Vitrectomy was performed on bilateral eyes of 15 pigmented rabbits.Porcine fibrin sealant kit of 0.5 ml was intravitreally injected in the lateral eyes of the rabbits as the experimental group,and equal volume of BSS was used at the same way in contralateral eye as control group.The inflammatory response of eye was observed under the slit lamp and ophthalmoscopy in 1 day,3,7,15,30 days after injection.Schi(o)tz tonometer was used to measure intraocular pressure(IOP) in 1 day,3,7 days,and retinal function was evaluated by electroretinogram (ERG) before operation and 30 days after operation.B-ultrasonic examination was carried out 30 days after surgery.Animals were sacrificed and eyeballs were obtained for retinal histopathological and ultrastructural examination in 30 days after operation.Results Complications appeared in 7 eyes of the experimental group,including cataract in 3 eyes,proliferation vitreoretinopathy and retinal detachment in 5 eyes,endophthalmitis in 1 eye,however,the cataract in 2 eyes and retina injury in 2 eyes were found in 15 control eyes.On the 30 days after injection,no inflammation was found in the 8 eyes without complication in the experimental group and 11 eyes in the control group.The IOP change was insignificant in different groups and various time points (Fgroup =0.008,P =0.929 ;Ftime =3.600 P =0.075).No significant difference was found in a-wave amplitude between groups and various time points(Fgroup =0.728,P =0.405 ; Ftime =0.516,P =0.482),and so was the b-wave amplitude (Fgroup =0.222,P =0.644 ; Ftime =0.057,P =0.814).On the 30th day after operation,arrangement of the retina was regular and no tissue edema and inflammatory cell infiltration were seen in both groups under the light microscope.Transmission electron microscope revealed that the ultrastructures of retinal cells,photoreceptor and retinal pigment cell were normal with the clear subcellular organelle,intact cellular membrane structure and mitochondria in both groups.Conclusions Domestic porcine fibrin sealant kit does not produce toxic effect on retina after intravitreal injection in rabbit.

Objective To investigate the effects of extracellular ATP on the expression of(Mi- crotubule associated proteins MAP-2)and the recovery of motor function after spinal cord injury in rats. Methods Six rats were selected randomly from 66 adult healthy Wistar rats as the normal control group,the rest animals were divided into two groups after contusion injury was performed by drop weight method with Allen impactor:Group A(ATP group)and Group B(control group),each group contained thirty rats.At days 1,3,7,14,and 28 after injury,the rats were killed,the expression of MAP-2 was detected with immunohistochemistry.The expression of MAP-2 in the adjacent area was quantitatively an- alyzed with a computer image analysis system.The recovery of motor function after spinal cord injury was assessed with improved Tarlov scores.Results The expression of MAP-2 was higher in Group A than in Group B after spinal cord injury in rats.Significant difference was revealed by the expression of MAP- 2 between the two groups at days 14 and 28 after injury(P

OBJECTIVETo establish a mice model of aminoglycoside antibiotics (AmAn) induced ototoxicity. Then to investigate the sensitivity of AmAn induced ototoxicity in three mouse strains and effect of kanamycin on the expression of Na-K-2Cl co-transporter-1 (NKCC1) in stria vascularis.

METHODSC57BL/ 6J, CBA/CaJ, NKCC1 +/- mice (each of twenty-four) were randomly divided into four experimental groups A, B, C and D (A kanamycin alone, B kanamycin plus 2, 3-dihydroxybenzoate, C 2, 3-dihydroxybenzoate alone, D control group). Mice were injected with kanamycin or/and 2, 3-dihydroxybenzoate for 14 days. Auditory function was measured by auditory brainstem response (ABR) and morphology of cochlea was observed by succinate dehydrogenase staining. Expression of NKCC1 was detected by immunohistochemistry.

RESULTSMice in group A developed significant ABR threshold shifts (P < 0.01), which were accompanied by out hair cells loss. Mice in group B significantly attenuated ABR threshold shifts with out hair cells loss (P <0.01). The immunostaining of NKCC1 in stria vascularis was attenuated significantly in group A compared with group D (P < 0.01) while the immunostaining in group B was enhanced than which in group A (P < 0.01). CBA/CaJ mice has the highest sensitivity to AmAn in three mouse strains.

CONCLUSIONSAn mouse model of AmAn induced ototoxicity could be established by administration of kanamycin. Kanamycin could inhibit the expression of NKCC1 in stria vascularis. 2, 3-dihydroxybenzoate could attenuate AmAn induced ototoxicity maybe by enhancing the expression of NKCC1. Mice that had the characteristic of presbycusis didn't show additional sensitivity of AmAn induced ototoxicity.

Animals ; Anti-Bacterial Agents ; toxicity ; Blood Vessels ; drug effects ; metabolism ; Cochlea ; blood supply ; drug effects ; metabolism ; Kanamycin ; toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Parabens ; toxicity ; Sodium-Potassium-Chloride Symporters ; metabolism ; Solute Carrier Family 12, Member 2

OBJECTIVETo explore the anti-aging effect of artemisia burning products (ie. smoke of moxibustion) and its proper intervention parameters.

METHODSAccording to factorial experiment design, 70 SAMP8 mice were randomly divided into one model group (group M) and 6 intervention groups: low concentration with 15 min group (group A1), low concentration with 30 min group (group A2), middle concentration with 15 min group (group B1), middle concentration with 30 min group (group B2), high concentration with 15 min group (group C1), high concentration with 30 min group (group C1). There were 10 cases in each group. Ten age-matched SAMR1 mice were used as normal group (group Z). All the mice in the 6 intervention groups were fumed with artemisia burning products of different concentration and time. The content of serum malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and glutathione reductase (GSH-Px) were tested.

RESULTSMDA content in group M was significantly higher than that in group Z (both P < 0.05), while SOD and GSH-Px activity were significantly lower in group M than that in group Z (both P < 0.05). Results of MDA, SOD and GSH-Px in 6 intervention groups were either of no statistically significant differences, or better than that in group M. Among 6 intervention groups, results of MDA and GSH-Px were better in group B1, while the result of SOD was better in group B2. Time factor didn't make any difference, while concentration of artemisia burning products is meaningful. As to SOD and GSH-Px, there's a strong interaction between the two factors.

CONCLUSIONWith certain concentration and time period, the intervention of artemisia burning products can exert anti-aging effect by increasing antioxydative capability and reducing metabolites of free radicals. Middle concentration and 30 minutes are recommended when intervened with artemisia burning products.

Aging ; blood ; metabolism ; Animals ; Antioxidants ; metabolism ; Artemisia ; chemistry ; Disease Models, Animal ; Glutathione Peroxidase ; blood ; Glutathione Reductase ; blood ; Humans ; Male ; Malondialdehyde ; blood ; Mice ; Moxibustion ; Superoxide Dismutase ; blood

OBJECTIVETo summarize the experiences of ligating left subclavian artery (LSA) in total arch replacement and stented elephant trunk implantation for Stanford type A aortic dissection patients with difficulty in exposing the LSA.

METHODSTotal arch replacement and stented elephant trunk implantation were performed on 79 consecutive patients from January 2008 to June 2010. Twenty-nine cases of the cohort undertook LSA ligation due to bad exposure. There were 21 males and 8 females patients, aged from 19 to 55 years with a mean of (44 ± 12) years. There were 12 acute dissections, 4 sub-acute dissections and 13 chronic dissections. Based on thoroughly evaluation of the Willis' circle and bilateral vertebral arteries through pre-operative imaging and intra-operative circulative parameters, if the collateral circulation was considered sufficient, LSA was ligated directly and only the innominate artery and carotid artery were reconstructed; if considered insufficient, an additional bypass from ascending aorta to left axillary artery was performed.

RESULTSAll the 29 operations were completed successfully. There was one patient died from pulmonary infection and the others recovered well.Blood pressure of left arms were lower than right postoperatively [(78 ± 17) mmHg vs. (126 ± 24) mmHg, 1 mmHg = 0.133 kPa, P < 0.01], but oxygen saturation, skin temperature and strength of the left hand were normal compared to the right. All the survived patients have been followed 1 - 27 months and none of them presented with any symptoms of left subclavian artery steal syndrome and ischemia of left arms.

CONCLUSIONSLigation of LSA under strict evaluation of collateral circulation could be safe in Type A dissection patients with bad exposure due to big ascending aortic aneurysm and will simplify the procedure significantly.

Adult ; Aneurysm, Dissecting ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Blood Vessel Prosthesis Implantation ; methods ; Female ; Follow-Up Studies ; Humans ; Ligation ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Subclavian Artery ; surgery ; Treatment Outcome ; Young Adult