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Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.
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Objective:To analyze the incidence of uveal effusion observed in primary glaucoma and explore the relevant factors.Methods:In this case control study, 692 primary glaucoma patients in the Second Hospital of Hebei Medical University from July 2016 to July 2017 were recruited, including 256 acute primary angle-closure glaucoma (APACG) patients, 368 chronic primary angle-closure glaucoma (CPACG) patients, and 68 primary open angle glaucoma (POAG) patients.Ultrasound biomicroscopy (UBM) was performed to determine the presence of uveal effusion, and to grade the effusion.The incidence of uveal effusion and the degree of effusion were analyzed statistically.The study protocol was approved by the Ethics Committee of the Second Hospital of Hebei Medical University.Results:The incidence levels of uveal effusion in the remission stage of APACG, the pre-clinical stage of APACG, and the progress stage of CPACG were 20.45% (54/264), 3.76% (8/213) and 1.45% (8/548), respectively; the incidence of uveal effusion among the three groups was statistically significant ( χ2=105.02, P<0.05). The incidence levels of uveal effusion in the pre-clinical stage of APACG and the progress stage of CPACG were obviously lower than that in the remission stage of APACG ( χ2=29.07, χ2=91.15; both at P<0.01). In the remission stage of APACG, the initial intraocular pressure was higher, and intraocular pressure fluctuation was larger in the patients with uveal effusion than that in the patients without uveal effusion, and these differences were statistically significant ( Z=-3.626, Z=-4.022; both at P<0.05). Uveal effusion was detected in 54 eyes of the 50 APACG patients in the remission stage, including Grade 3 in 16 eyes, Grade 2 in 12 eyes, and Grade 1 in 26 eyes.Uveal effusion was demostrated in eight eyes of eight patients in the preclinical stage of APACG, and all at Grade 1.In the progress stage of CPACG, uveal effusion was also revealed in eight eyes of eight patients, all at Grade 1.In the remission stage of APACG, the degree of effusion was positively correlated with the initial intraocular pressure and the fluctuation of intraocular pressure ( r s=0.912, r s=0.923; both at P<0.01). However, the degree of effusion was inversely associated with intraocular pressure after treatment ( r s=-0.269, P<0.05). Conclusions:Uveal effusion can be observed in the remission and preclinical stages of APACG, and in the progress stage of CPACG.The remission stage of APACG shows both the highest rate and the severest degree of this complication.The degree of effusion is positively correlated with the initial intraocular pressure and the decrease in intraocular pressure, but it is inversely associated with intraocular pressure after treatment.
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Objective To measure quantitatively and analysis the differences in the anterior segment biological parameters between the normal subject and patients suffering primary angle closure glaucoma (PACG),as well as the distinction among different stages of PACG by using anterior segment optical coherence tomography (OCT).Methods A retrospective case series study was designed.Medical records of 217 cases (217 eyes) from The Second Hospital of Hebei Medical University from December 2013 to December 2014 were recruited,including 5 groups as follows:35 cases (35 eyes) with pre-clinical stage acute primary angle closure glaucoma (APACG),32 cases (32 eyes) with remission period of APACG,35 cases (35 eyes) with early stage of chronic primary angle closure glaucoma (CPACG),35 cases (35 eyes) with progress period of CPACG and 80 cases (80 eyes) coming for regular eye health examination in general clinic.The anterior segment biological parameters of each group was measured by Heidelberg Spectralis OCT,including the anterior chamber width (ACW),angle opening distance (AOD),trabecular iris area (TISA),iris thickness (IT) and crystalline lens rise (CLR).Results The IT and CLR of APACG and CPACG were significantly greater than normal control group,while other anterior segment parameters were significantly smaller,with significant differences between them (all at P＜0.01).The IT and CLR of APACG was bigger than those of CPACG,with significant differences between them (both at P＜0.05),the ACW,AOD,TISA of the two gruops showed no significant differences.The AOD and TISA of remission period of APACG were significantly decreased than those of pre-clinical stage (all at P＜O.01).The IT and CLR of remission period APACG was significantly greater than pre-clinical stage (both at P＜0.01).The difference in ACW of the two group was not statistically significant (P＞0.05).Compared with progress period of CPACG,the IT of the early stage of CPACG was thicker,while the CLR was smaller (both at P＜0.01).There was no significant difference in ACW,AOD and TISA between the two groups.The IT2000 and ITmax of pre-clinical stage of APACG were significantly smaller than those of early stage of CPACG (both at P＜0.01).There was no significant difference in other parameters between the two groups (P＞0.05).The IT750,IT2 000 and ITmax of the pre-clinical stage of APACG were significantly thicker than those of progress period of CPACG (all at P＜0.05).There was no significant difference in other parameters between the two groups (P＞0.05).Conclusions Compared with normal people,the PACG patients have a more crowding anterior segment structure,smaller AOD,smaller TISA,thicker IT and more anterior located lens.The APACG patient at remission period has a more crowding anterior segment structure,smaller AOD,smaller TISA,thicker IT and more anterior located lens than APACG patient at per-clinic stage.The CPACG patient at progress period has a higher CLR,but thinner IT than patient at early stage.The APACG patients at per-clinic stage has thicker IT and a more crowding anterior segment structure than the CPACG patient at early stage,and the APACG patient at remission period has thicker IT than CPACG patient at progress period.
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Objective To evaluate the relationship between spinal Sonic hedgehog (Shh) signaling pathway and inflammatory responses in rats with neuropathic pain (NP).Methods Forty-eight cleangrade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table method:sham operation group (group S),group NP,dimethyl sulfoxide (DMSO) group (group D) and specific Shh signaling pathway inhibitor cyclopamine group (group CP).Spared nerve injury was produced by exposing the sciatic nerve and branches followed by ligation and transection of tibial and common fibular nerves in anesthetized rats.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before establishing the model and 1 and 7 days after establishing the model.,The animals were sacrificed after measurement of pain threshold at 7 days after operation,and the lumbar segment L4-6 of the spinal cord was obtained for determination of the expression of Shh,Patched homolog (Ptch),Smoothened (Smo) and zinc finger-containing transcription factors 1 (Gli1) (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) (by enzyme-linked immunosorbent assay).Results Compared with group S,the MWT was significantly decreased,the expression of Shh,Patched,Smo and Gli1 was up-regulated,and the contents of TNF-α and IL-1β were increased in NP,D and CP groups (P＜0.05).Compared with group NP,the MWT was significantly increased,the expression of Shh,Patched,Smo and Gli1 was down-regulated,and the contents of TNF-α and IL-1β were decreased in group CP (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＜0.05).Conclusion The mechanism by which Shh signaling pathway is involved in the development and mainterance of inflammatory responses is related to inhibiting inflammatory responses of the spinal cord in rats with NP.
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Bone mesenchymal stem cells (BMSCs) have been used worldwide to treat spinal cord injury, but their therapeutic mechanism is poorly understood. In this study, BMSCs were transplanted to aneurysm clip-injured rats to demonstrate their protective effect. We observed myelin sheaths through Luxol fast blue (LFB) staining, osmic acid staining, TUNEL and transmission electron microscopy (TEM). We performed Western blotting to analyze the expressions of brain-derived neurotrophic factor (BDNF) and caspase 3. BMSCs were transplanted at 1, 7 and 14 days after spinal cord injury. Hindlimb movement (Basso, Beattie and Bresnahan; BBB) score, CNPase (2', 3'-cyclic-nucleotide 3'-phosphodiesterase), myelin basic protein (MBP) and caspase 3 protein levels were detected. Immunofluorescence was used to test the differentiation of BMSCs after implanted into damaged spinal cord and co-expression of CNPase-caspase 3+. At 7 days after BMSCs transplantation, some injected BMSCs expressed neuronal and oligodendrocyte markers. And both locomotor skills and ultra-structural features of myelin sheaths were significantly improved. The expressions of BDNF were clearly increased by BMSCs transplantation, the expression of caspase 3 was the opposite. Compared with the 1 and 14 days transplantation after spinal cord injury, MBP and CNPase expressions were highest, caspase 3 expression was lowest in 7 days BMSCs transplantation. After BMSCs transplantation, CNPase-caspase 3+ cells scattered in the white matter of the spinal cord. Therefore, BMSCs had a tendency to differentiate into neurons and oligodendrocytes after transplantation, which could promote the secretion of BDNF. BMSCs protected neural myelin sheaths by inhibiting oligodendrocyte apoptosis via increased secretion of BDNF after SCI. The best therapeutic time was 7 days after spinal cord injury.
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Background Cornea astigmatism can be effectively corrected by implanting Toric intraocular lens (IOL) during cataract surgery and therefore improve visual acuity of patients.However,the decentration and rotation position errors were inevitable sometime.What's the difference of effect of position errors on quality of image between spherical IOL and Toric IOL needs further research.Objective This study was to evaluate the optical performance and wavefront with rotation and decentration of Toric IOL.Methods Different decentration for SN60AT IOL(spherical IOL) and Toric IOL in Hwey-Lan Lion model eyes was set with the role as follows:decentration 0.25 mm to 0.75 mm in a 5°-interval from 0° to 90°.Furthermore,Toric IOL was rotated at 5° and 10°,respectively.Then the image performances of SN60AT IOL and Toric IOL at different decentration distances and rotated degrees were evaluated with modulation transfer function (MTF) and value of wavefront aberration under all conditions.Results At the centration,the MTF curves of spherical IOL and Toric IOL were similar under 3,4 and 5 mm pupil diameter at each spatial frequency.Under the condition of 4 mm pupil diameter,when the decentration was 0.25 mm,the MTF values of SN60AT IOL at 6 c/d and 12 c/d were 0.581 087 and 0.411 960,respectively.T3 IOL were 0.454 259 and 0.382 313,T4 IOL were 0.426 020 and 0.360 490,T5 IOL were 0.425 606 and 0.359 877.When the decentration was 0.50 mm,the MTF values of SN60AT at 6 c/d and 12 c/d were 0.573 073 and 0.412 787,respectively.T3 IOL were 0.450943 and 0.379481,T4 IOL were 0.423 153 and 0.356 664,T5 IOL were 0.422 881 and 0.356 230.When the decentration was 0.75 mm,the MTF values of SN60AT at 6 c/d and 12 c/d were 0.560 038 and 0.413 624,respectively.T3 IOL were 0.445 597 and 0.374 322,T4 IOL were 0.418 522 and 0.350 087,T5 IOL were 0.418 468 and 0.349 976.When the IOL decentralized along 0°,5°,10°,90°meridian line,the MTF values were almostly same.The root mean square (RMS) of spherical IOL and Toric IOL was increased when the IOL decentralized from 0 mm to 0.75 mm,with the most increasing level in coma aberration and slight increase in trefoil aberration.When the T4 IOL decentralized from centre to 0.75 mm,the coma increased from 0 to C(3,-1)-0.049 79 μm,C (3,1)-0.037 59 μm and the trefoil aberration increased from 0 to C (3,3) 0.005 72 μm,C (3,-3) 0.004 64 μm.With the increase of rotation degrees (from 5°to 10°) of Toric IOL,the MTF was worse at high spatial frequency.Toric IOL rotation caused the increase of astigmatism and residual astigmatism and spherical error,but not high order aberration.Conclusions The tolerance of Toric IOL to decentration is very close to the spherical IOL,and optical performance is only associated with the amount of decentration but not direction.The aberration caused by Toric IOL decentration is mainly coma.The rotation of Toric IOL causes astigmatism error but not high order aberrations.
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Background The residual astigmatism following Toric intraocular lens (IOL) rotation have received much attention.However,the variation of the optical performance and the wavefront abrrveation with Toric IOL rotation are unclear.Objective The aim of this study was to evaluate the optical performance,wavefront abrrveation and residual diopter spherical and cylinder lens with Toric IOL rotation.Methods T3,T4 and T5 Toric IOLs of +22.0 D were placed in Hwey-Lan Liou model eye respectively,with the posterior surface flat on the X axis and steep on the Y axis.Corneal astigmatism model was established by mimicing the model eye with Toric IOL using Zemax optical software.Then the Toric IOLs were rotated 5° to 10° individually under the 4 mm pupil diameter and 550 nm monochromatic light,and the image performance and wavefront abrrveation were recorded with all conditions,including modulation transfer function (MTF),out-of-focus aberration,astigmatism aberration,coma,trefoil aberration and spherical aberration.The refractive error of spherical power and cylinder power were calculated.Results Corneal astigmatism was fully corrected when Toric IOLs in the middle,and the MTF curves were near in T3,T4,T5 Toric IOLs.The image performance was worse under the high spatial frequency with the increase of rotation degrees of Toric IOLs,showing the gradually low of MTF curves,especially T5 Toric IOL.No obvious changes was seen in coma,trefoil aberration and spherical aberration after rotation of Toric IOLs,while out-of-focus aberration,astigmatism aberration were obviously increased.In addition,residual astigmatism and spherical error increase with the rotation of Toric IOLs.Conclusions Toricl IOL rotation leads to increase of astigmatism and spherical refractive error but not high order aberration.
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Objective To evaluate the changes in the expression of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the spinal cord of rats with neuropathic pain.Methods Fifty-four healthy adult male Sprague-Dawley rats,weighing 250-300 g,were divided into 2 groups (n=27 each) using a random number table:sham operation group (S group) and neuropathic pain group (NP group).Neuropathic pain was produced by chronic constriction injury in anesthetized rats.The sciatic nerve was exposed,and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4.0 chromic catgut.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 1,4,7 and 14 days after operation.After measurement of MWT at each time point after operation,the animals were sacrificed,and the L4_6 segments of the spinal cord were removed for determination of the expression of NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),caspase-1 and interleukin-1beta (IL-1β) protein and mRNA (by Western blot or by fluorescent quantitative real-time polymerase chain reaction).After measurement of MWT at day 14 after operation,the L4-6 segments of the spinal cord were removed for determination of the co-expression of NLRP3 with glial fibrillary acidic protein (GFAP) (by double immunofluorescence staining).Results Compared with S group,the MWT was significantly decreased,and the expression of NLRP3,ASC,caspase-1 and IL-1β protein and mRNA was up-regulated at each time point after operation in NP group (P＜0.05).The expression of NLRP3 and ASC protein and mRNA peaked at day 4 after operation,the expression of caspase-1 and IL-1β protein and mR-NA peaked at day 7 after operation,and the MWT reached the lowest value at day 7 after operation (P＜0.05).NLPR3 inflammasomes were mainly expressed in the astrocytes and neurons.Conclusion The expression of NLPR3 inflammasomes in the spinal astrocytes and neurons is up-regulated in the rats with peripheral nerve damage,and the change may be involved in the development and maintenance of neuropathic pain.
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Background Interleukin-1β (IL-1β) is an important inflammation-related factor in the initial stage of proliferative vitreoretinopathy (PVR).The previous research showed that curcumin can inhibit IL-1 β-induced proliferation of rabbit retinal pigment epithelium (RPE) cells,but the anti-inflammatory mechanism and effect of curcumin are still undefined.Objective This study was to observe the migration of IL-1β-induced rabbit RPE cells,and evaluate the function and mechanism of inhibition of curcumin on IL-1β-induced inflammation of RPE cells.Methods Cultured rabbit RPE cells of generation 4 were used in this experiment.The cells were cultured in serum-free DMEM and 0,0.1,1.0 and 10.0 μg/L IL-1β were separately added in the medium for 24 hours.The expressions of cyclooxygenase-2 (COX-2) protein and mRNA in the cells were detected by Western blot and reverse transcription PCR to determine the optimal concentration of IL-1β.The cells were divided into IL-1β group and curcumin+IL-1β group,and 1.0 μg/L IL-1 or 1.0 μμg/L IL-1 β combined with 10 μg/ml curcumin was respectively added into the medium for 24,48 and 72 hours.The cells cultured by only serum-free medium served as the control group.Hematoxylin and eosin staining was conducted for the cells to count the number of cells migrating into the injured area under the optical microscope.The relative expression levels of COX-2 protein and mRNA in the cells were detected by Western blot and reverse transcription PCR,and the relative expression levels of nuclear factor (NF)-κBp65 and inhibitor of NF-κB-α (IκB-α) protein were also detected by Western blot assay.The expression intensity and location of NF-κBp65,IκB-α and COX-2 in the cells were detected by immunochemistry.Results RPE cells just isolated from the rabbit eyes were in round shape and abundant in melanin.The melanin significantly decreased in the fourth generations of RPE cells.The shape of cells became long and narrow,and net shaped distribution.Immunochemistry demonstrated the strong positive response of RPE cells for keratin (AE1/AE3).There were (31.93 ±1.21),(36.27±2.50) and (38.33±2.40) migratory cells in the control group after 24,48 and 72 hours respectively.The number of migratory cells increased to 45.73 ± 2.30,71.13 ± 1.92 and 80.60 ± 1.71 in the IL-13 group,but obviously decreased to 13.13 ± 2.20,14.93 ± 1.10 and 12.60 ± 1.51 in the curcumin + IL-1β group.A Significant increase in the migrating cell number was found in the IL-1 β group compared with the control group and the curcumin+IL-1β group in various time points (all at P＜0.05).The relative expression levels of COX-2 protein and mRNA peaked in the 1.0 μg/L IL-1β group,so 1.0 μg/L of IL-1β was determined as the optimal concentration in the experiment.In 24,48 and 72 hours after culture,the expression levels of COX-2 protein and mRNA in the cells were significantly lower in the curcumin + IL-1β group than those in the control group (all at P＜0.05).The relative expression level reached peak in NF-κBp65 protein and lowed bottom in IκB-α proteins at 48 hours after cultured in the IL-1β group,and the reverse trend was seen in the curcumin+IL-1β group,with the significant differences between the two groups (both at P＜0.05).Immunochemistry showed that NF-κBp65 was expressed strongly in the cell nuclei and cytoplasm in the IL-1 β group and presented the weaker expression in the control group and the curcumin+IL-1 β group.Compared with the control group,the expression was weaker in IκB-α and stronger in COX-2 in the IL-1β group.In addition,the expression of IκB-α was enhanced and that of COX-2 was attenuated in the curcumin+IL-1β group in comparison with the IL-1β group.Conclusions Curcumin inhibits the movement of rabbit RPE cells induced by IL-1β.IL-1β up-regulates the expression of COX-2 by activating NF-κB signal pathway,and curcumin plays an anti-inflammatory role by blocking this pathway.
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Background Pentacam anterior segment analysis system (Pentacam) is more accurate in the quantitative evaluation of ocular anterior segment in primary angle-closure glaucoma (PACG) eyes than slit lamp microscope and ultrasound biomicroscope (UBM).However,its accuracy in the earlier stage of PACG before and after YAG laser peripheral iridotomy (LPI) is not fully elucidated.Objective This study was to assess the effect of YAG LPI in PACG patients with Pentacam.Methods A prospective self-controlled study was performed.Thirtyfive fellow eyes (pre-clinical stage of PACG) of acute PACG and 35 fellow eyes of chronic PACG were included in the Second Hospital of Hebei Medical University from July,2012 to December,2013.YAG LPI was performed on the eyes,and the parameters of ocular anterior segment including central anterior chamber depth (ACD),anterior chamber volume (ACV) and peripheral anterior chamber angle (ACA) were measured and compared by Pentacam before and 1 day,7 days,28 days after operation.This study was approved by the Ethic Committee of the Second Hospital of Hebei Medical University and informed consent was obtained from all subjects.Results In pre-clinical stage of PACG eyes,the postoperative ACD and ACV values were increased in comparison with preoperation,showing significant differences among various time points (ACD:F =6.783,P =0.004;ACV:F =19.090,P =0.000),and no significant difference was found in ACA among different time points (F =0.153,P =0.928).In the fellow eyes of chronic PACG,the postoperative ACD and ACV values were larger than those of preoperation,with significant differences among various time points (ACD:F =21.576,P =0.000;ACV:F =47.506,P =0.000),and no significant difference was found in ACA among different time points (F=0.581,P=0.629).The change values of ACD and ACV were (0.064±0.022) mm and (27.840±4.963) mm3 in the eyes of pre-clinical stage of PACG,and those in the fellow eyes of chronic PACG were (0.047-± 0.020) mm and (21.000 ± 3.278) mm3,showing significant differences between the two groups (ACD:t=2.783,P=0.008;ACV:t=5.749,P=0.000).Conclusions Pentacam allows easy,fast,automatic and non-contact quantification and three-dimension image of the anterior chamber parameters before and after YAG LPI in pre-clinical stage of PACG eyes and fellow eyes of chronic PACG.The ACD deepens and ACV increases after LPI in glaucomous eyes,especially in the pre-clinical stage of PACG eyes.
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Background Proliferative vitreoretinopathy (PVR) is a common cause of vision loss clinically,and retinal pigment epithelium (RPE) cells play a major part in this disease.Studying the effect of traditional Chinese medicine on RPE cells are of great importance to reveal the pathogenesis and prevention of PVR,which were rarely reported.Objective This study was to study and compare the inhibition effect among curcumin,salvia miltiorrhiza and matrine on IL-1β-induced proliferation of rabbit RPE cells.Methods RPE cells at passages 3-4 were enrolled for the research and identified by transmission electron microscope.The proliferation effect of IL-1 β (2.5,5.0,10.0,20.0 μg/L) and inhibitory effect of curcumin (5,10,20 μg/ml),salvia miltiorrhiza (5,10,20 μg/ml)or matrine (100,200,400 μg/ml) on RPE cells 24,48 and 72 hours after cultivation were studied by MTT assay.The 50％ inhibitory dose (IC50) of the three medicines were analyzed by regression analysis.The use and feeding of the experimental animals were followed by the ARVO Statement.Results RPE cells isolated from the rabbit eye were in round shape and abundant in melanin;The melanin significantly decreased in the fourth generations of RPE cells.Immunohistochemistry showed that the RPE cells was positive for keratin (AE1/AE3).The proliferation rates of RPE cells were statistically different among different concentrations of IL-1β 24,48 and 72 hours after cultivation (Ftime =30.33,P =0.00;Fconcentration =9.37,P =0.00);The proliferation rates of RPE were significantly different among different time points or different concentrations of IL-1β (all at P ＜ 0.05).And the proliferation rate run up to maximum at 10 μg/L after 72 hours of cultivation.The inhibitory rates of the three medicines were statistically different among different time points or different concentrations (curcumin:Ftime =128.75,P =0.00;Fconcentration =334.05,P=0.00.salvia miltiorrhiza:Ftime =39.32,P=0.00;Fconcentration =165.57,P=0.00.matrine:Ftime =267.76,P =0.00;Fconcentration =912.34,P =0.00).The three medicines dose-dependently and time-dependently inhibit IL-1β-induced proliferation of RPE cells,with significant differences between the adjacent time points and concentrations (all at P＜0.05).The IC50 were 26.77,19.01 and 9.45 μg/ml for curcumin;33.72,23.47 and 12.56 μg/ml for salvia miltiorrhiza,570.96,352.25 and 97.50μg/ml for matrine 24,48 and 72 hours after cultivation.Conclusions The proliferation of RPE cells can be stimulated by IL-1β,and the maximal proliferation occurred with a concentration of 10.0 μg/L IL-1β.Curcumin,salvia miltiorrhiza and matrine dose-dependently and time-dependently inhibit proliferation of RPE cells induced by IL-1β.Curcumin is the best medicine to inhibit the proliferation of RPE cells.
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Background The optic quality of Toric intraocular lens (IOL)-implanted eye is affected by the residual astigmatism and individual difference of corneal spherical aberration and different magnification from steep and flat axis refraction.Whether correcting Toric IOL spherical aberration can effectively improve the image quality of individual patient is a question to be studied.Objective This study attempted to collect eye parameters of cataract patients to reconstruct the customized vision model by using Zemax optical software,and to evaluate the image performance with different Toric IOL spherical aberration.Methods A prospective study was performed.Forty-five eyes of 45 cataract patients were included in Second Hospital of Hebei Medical University from August 2012 to October 2013.Several relevant parameters were measured by Pentacam,including anterior and posterior surface height of cornea,corneal thickness,curvature radius of flat and steep meridians of anterior surface astigmatism,refractive diopter and curvature radius of posterior surface.The astigmatism of anterior and posterior corneal surface was described by Matlab 4.5 software.Corneal astigmatism model were set as aspheric state,and the effective position of Toric IOL was calculated using Holladay Ⅰ formula.Customized individual model eyes were constructed by Zemax software.The contrast sensitivity function (CSF) of different spherical Toric IOLs at different spatial frequencies were calculated and compared between 300 Td light environment with 3 mm pupil diameter (photopia light) and 0.3-1.0 Td light environment with 5 mm pupil diameter (mesopia light).This study was approved by Second Hospital of Hebei Medical University ethics committee,all the patients signed the informed consent.Results The mean astigmatism power was (1.51 ± 0.36) D and (1.49 ± 0.37) D,and the mean astigmatism meridian was (101.5 ± 59.8) ° and (101.9±58.5) ° in the model eyes and cataract eyes,respectively,without significant differences between them (t=0.886,0.652;both at P＞0.05).Bland-Altman test showed a good agreement in astigmatism power and astigmatism meridian between model eyes and cataract eyes.The LogCSF values at 1.5,3.0,6.0,12.0 and 18.0 c/d spatial frequencies were significantly higher in the aspherical Toric IOL model eyes than those in the spherical Toric IOL model eyes,and the LogCSF values at various spatial frequencies were significantly higher in the Toric IOLs with spherical aberrations of-0.13 μm and-0.26 μm than those in the zero spherical aberrations in both photopia light and mesopia light (all at P＜0.05).Conclusions A precise corneal astigmatism model based on cornea high data of cataract eyes was successfully constructed through special formulas with Zemax software.Aspherical Toric IOL can compensate for spherical aberration of cornea and enhance the optic quality in individual model eye.
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Objective To evaluate the role of Sonic hedgehog (Shh) signaling pathway in the spinal cord in neuropathic pain (NP) in the rats.Methods Seventy-two male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 2 groups (n=36 each) using a random number table:sham operation group (S group) and NP group.Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized rats.The mechanical paw withdrawal threshold (MWT) was measured before operation and at 1,4,7,14 and 21 days after operation.After measurement of the pain threshold at 1,4,7,14 and 21 days after operation,the animals were then sacrificed,and the lumbar segment (L46) of the spinal cord was obtained for determination of Shh,Patched (Ptch),Gli1 and glial fibrillary acidic protein (GFAP)expression (by Western blot),Shh,Ptch and Gli1 mRNA expression (by fluorescent quantitative real-time reverse transcriptase-polymerase chain reaction),and Shh and GFAP expression (by immunohistochemistry).Results Compared with group S,the MWT was significantly decreased,and the expression of Shh,Ptch and Gli1 protein and mRNA and GFAP in spinal cord tissues was up-regulated in group NP (P＜ 0.05).Shh was mainly expressed in the cytoplasm of spinal dorsal horn neurons and in the gap around glial cells.Conclusion Shh signaling pathway in spinal cord is involved in the development and maintenance of NP in the rats.
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Objective To compare the low-intensity focused ultrasound (LIFU) and high-intensity focused ultrasound (HIFU) in treating pain due to chronic soft tissue injury.Methods Ninety-three patients with pain due to chronic soft tissue injury, aged 18-80 yr, with body mass index of 18-31 kg/m2,course of the disease 3 months-10 yr, and pain intensity of 4-8 in a numeric rating scale, were randomly divided into 2 groups using a random number table: low intensity group (group LI, n =49) and high intensity group (group HI, n =44).In group LI, the patients received LIFU with the minimum ultrasonic intensity causing senses (acid, hemp, swelling, pain) , and the treatment was continued for 10 min.In group HI, the patients received HIFU with the focused uhrasound intensity that could not be tolerated by the patients, the treatment was continued for 1 min each time and then suspended for 1 min, and the total time for treatment was 10 min.The patients received the treatment once a day, and the course of treatment was 5 days in both groups.When numeric rating scale score ＞ 4 during the treatment, parecoxib sodium 40 mg was injected intramuscularly as rescue analgesic.Both the therapeutic index and improvement in movement were used to evaluate the therapeutic effect, and the quality of life and depression were assessed and scored.The treatment-related adverse events were also recorded.Results The total effective rate was 98％ and 84％ in LI and HI groups, respectively.Compared with group HI, the total effective rate was significantly increased, the quality of life score was increased, and no significant change was found in depression score in group LI.No patients used parecoxib sodium or developed treatment-related adverse events in group LI.One patient (2％) required parecoxib sodium, the incidence of skin burns, nerve damage and abnormal pain was 4％, 2％ and 2％, respectively, and no patients developed tissue swelling in group HI.Conclusion LIFU has higher therapeutic effect than HIFU in treating pain due to soft tissue injury, and the safety is good.
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Objective To evaluate the effect of spinal cord stimulation (SCS) on the expression of spinal substance P (SP) and calcitonin gene-related peptide (CGRP) in rats with neuropathic pain.Methods Forty-eight male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were randomly divided into 4 groups (n =12 each) using a random number table: sham operation group (S group) , n europathic pain group (group NP), sham electrical stimulation group (N-SCS group) , and SCS group.Neuropathic pain was induced by chronic constriction injury (CCI) in anesthetized rats.The sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut.Electrodes were placed into the epidural space at 5 days after CCI in N-SCS and SCS groups, and in addition, SCS was performed at 12-14 days after CCI in SCS group.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before CCI, and 1, 4, 7 and 14 days after CCI.After measurement of pain threshold at day 14 after CCI, the animals were sacrificed, and the lumbar segments (L4-6) of the spinal cord were obtained for determination of the expression of SP and CGRP in the spinal cord by immunohistochemistry.Results Compared with group S, the MWT was significantly decreased, and the expression of SP and CGRP protein and mRNA was up-regulated in NP, N-SCS and SCS groups (P＜0.05).Compared with group NP, the MWT was significantly increased, and the expression of SP and CGRP protein and mRNA was down-regulated in group SCS (P＜0.05).Conclusion The mechanism by which SCS mitigates neuropathic pain may be related to down-regulated expression of SP and CGRP in the spinal cord of rats.
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Objective To investigate the relationship between the mechanism of mitigation of neuropathic pain by spinal cord stimulation (SCS) and high mobility group protein box-1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway in the spinal cord of rats.Methods Forty-eight male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 4 groups (n =12 each) using a random number table:sham operation group (S group),chronic constrictive injury (CCI) group,sham SCS group (S-SCS group),and SCS group.Neuropathic pain was induced by CCI in the animals anesthetized with intraperitoneal chloral hydrate.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.Electrodes were placed into the epidural space at 5 days after CCI in S-SCS and SCS groups,and in addition SCS was performed at 12-14 days after CCI in SCS group.Paw withdrawal threshold to mechanical stimulation (MWT) were measured at 1 day before operation and 1,4,7,14 days after CCI.After measurement of pain threshold at day 14 after CCI,the animals were sacrificed and the lumbar segments (L4-6) of the spinal cord were obtained for determination of mRNA expression of HMGB1,TLR4,and NF-κB p65 (in the nuclear protein,by real-time fluorescent quantitative PCR),protein expression of TLR4 and NF-κBp65 (by Western blot),and protein expression of HMGB1 (by immunohistochemistry).Results Compared with S group,MWT was significantly decreased after CCI,the mRNA and protein expression of HMGB1 and TLR4 was up-regulated,and the expression of NF-κB p65in the nuclear protein and mRNA was up-regulated in CCI,S-SCS and SCS groups.Compared with CCI group,MWT was significantly increased after spinal cord stimulation,the mRNA and protein expression of HMGB1 and TLR4 was down-regulated,and the expression of NF-κB p65 in the nuclear protein and mRNA was down-regulated in SCS group.Conclusion The mechanism by which SCS mitigates neuropathic pain may be related to inhibition of HMGB1/TLR4/NF-κB signaling pathway in the spinal cord of rats.
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Objective To evaluate the effect of celastrol postconditioning on focal cerebral ischemiareperfusion (I/R) injury in rats.Methods Sixty-four Sprague-Dawle rats (32 males,32 females),weighing 250300 g,were randomized into 4 groups using a random number table (n =16 each):sham operation group (group S) ; celastrol control group (group S + C) ; focal cerebral I/R group (group I/R) ; celastrol postconditioning group (group I/R + C).Focal cerebral I/R were produced by middle cerebral artery occlusion (MCAO).Dimethyl sulfoxide (DMSO) 0.3 ml/kg was injected intraperitoneally after shame operation in group S.Celastrol 3 mg/kg was injected intraperitoneally after shame operation in group S + C.DMSO 0.3 ml/kg was injected intraperitoneally at 5 min of reperfusion in group I/R.Celastrol 3 mg/kg was injected intraperitoneally at 5 min of reperfusion in group I/R + C.The neurologic deficit was scored at 5 min before reperfusion and 24 h of reperfusion.The infarct size was detected by TTC staining,and then the percentage of infarct size was calculated.The pathological changes in CA1 region of ischemic hippocampus were detected by HE staining.The activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX),content of reactive oxygen species (ROS) and expression of NOX1 and NOX2 mRNA (by RT-PCR) in ischemic brain tissues were detected.Results Compared with S and S + C groups,the neurologic deficit scores,infarct size,percentage of infarct size,NOX activity and ROS content were significantly increased,and the expression of NOX1 mRNA and NOX2 mRNA was up-regulated in I/R and I/R + C groups (P ＜ 0.01).Compared with group I/R,the neurologic deficit scores,infarct size,percentage of infarct size,NOX activity and ROS content were significantly decreased,and the expression of NOX1 mRNA and NOX2 mRNA was down-regulated in group I/R+ C (P ＜ 0.01).There was no significant difference in the parameters mentioned above between group S and group S + C (P ＞ 0.05).The pathological changes in CAl region of ischemic hippocampus were significantly attenuated in group I/R + C (P ＜ 0.01).Conclusion Postconditioning with celastrol can auenuate focal cerebral [/R injury in rats and inhibiton of oxidative stress response in brain tissues may be involved in the mechanism.
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Background The anti-proliferative effect of matrine has been demonstrated and its relevance to prevention and treatment of proliferative retinovitreopathy is concerned.Howeverthe intravitreous injection of free-matrine reiteratively may raise the risk of ocular infection.ObjectiveThe goal of the present study is to investigate the sustained releasing ability and safety of matrine polyactic acid microsphere(MAT-PLA-MSintravitreal injection.MethodsMAT-PLA-MS was prepared by Hebei Medical University and examined under the transmission electron microscope.The release of MAT-PLA-MS was monitored by ultraviolet spectrophotometry.Free-matrine with the dose of 1,2,4mg was intravitreally injected respectively in 12 eyes of New Zealand albino rabbits in free-matrine group and MAT-PLA-MS with matrine(2,4,6mg respectively was administered in 16 eyes separately in matrine microsphere group.The blank microsphere was injected in 6 right eyes as blank control group and normal saline solution was injected in 6 fellow eyes as control group.The retinal function change was evaluated by electroretinogram(ERG),and the morphological and histological change of retina following drug injection were assessed under the slit lamp biomicroscope,indirect ophthalmoscope,light microscope and transmission electron microscope.The decomposed process of MAT-PLA-MS in vitreous was recorded with ocular anterior segment and fundus color camera.Results MAT-PLA-MS containing matrine showed the spherical shape with the mean diameter of 2.28±47μm under the transmission electron microscope and the drug-loading rate 6.17% and drug-release rate 87.93% in vitro for 672 hours,presenting the controllable release characteristics.After implantation into the vitreous,the MAT-PLA-MS containing matrine decomposed gradually with the prolong of time.The b amplitudes of ERG maximum response were significantly declined in 4mg free-matrine injection group in comparison with before injection in various time points(P<0.01).However,no considerably differences were found in MAT-PLA-MS with matrine groups and control groups in various time points following the intravitreal injection(P>0.05).No obvious abnormal was seen under the slim lamp and ophthalmoscope through the study period.The changes of retinal ultrastructure were found from 1 through 28 days after injection of 4mg free-matrine,and slight retinal structural damage was seen from 7 through 28 days after injection of 6mg MAT-PLA-MS containing matrine.ConclusionThese results suggest that MAT-PLA-MS possesses good sustained release feature.MAT-PLA-MS containing matrine has less toxicity to retina than free-matrine after intravitreal injection.MAT-PLA-MS is an excellent drug delivery system.
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Objective To investigate the effect of parecoxib pretreatment on focal cerebral ischemia-reperfusion (I/R) injury in rats. Methods Sixty-four male SD rats weighing 250-300 g were randomly divided into 4 groups ( n= 16 each): sham operation group (group S); focal cerebral I/R group; focal cerebral I/R + parecoxib 5 mg/kg group (group P5); focal cerebral I/R + parecoxib 10 mg/kg group (group P10). Focal cerebral I/R was produced by occlusion of middle cerebral artery for 2 h followed by 24 h of reperfusion. Parecoxib 5 and 10 mg/kg were injected intravenously through the internal jugular vein 30 min before ischemia in group P5 and P10 respectively. The neurologic deficit scores (NDSs) were measured at 24 h of reperfusion and then the rats were decapitated.Brains were rapidly removed for determination of the infarct volume, apoptosis rate and expression of Bcl-2 and Bax. The ratio of Bcl-2 to Bax (Bcl-2/Bax) was calculated. Results The NDSs, apoptosis rate and expression of Bcl-2 and Bax were significantly higher, Bcl-2/Bax was significantly lower, and the infarct volume was significantly larger in group I/R than in group S ( P ＜ 0.01 ). The NDSs were significantly lower in group P10, and the apoptosis rate and Bax expression were significantly lower, the infarct volume was significantly smaller, Bcl-2 expression and Bcl-2/Bax were significantly higher in group P5 and P10 than in group I/R (P ＜0.05 or 0.01). The infarct volume was significantly smaller, the apoptosis rate and Bax expression were significantly lower, and Bcl-2 expression and Bcl-2/Bax were significantly higher in group P10 than in group P5 ( P ＜ 0.05 or 0.01 ). Conclusion Pretreatment with parecoxib can attenuate focal cerebral I/R injury in a dose-dependent manner through inhibition of cell apoptosis via up-regulation of Bcl-2 expression and down-regulation of Bax expression in rats.
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Objective To investigate the effects of simvastatin pretreatment on ischemia-reperfusion (I/R)injury to the spinal cord in rats. Methods Ninety-six healthy male SD rats weighing 220-280 g were randomly divided into 3 groups (n=32 each): Ⅰ group sham operation (group S); Ⅱ group I/R and Ⅲ group simvastatin pretreatment (group Si). The animals were anesthetized with 10% chloral hydrate 0.4 ml/100g. I/R to the spinal cord was induced by cross-clamping the aorta below renal artery for 45 min followed by reperfusion according to Zivin in group Ⅱ and Ⅲ. In group Ⅲ simvastatin 20 mg/kg was administered via gastric tube in the morning for 3 days before operation. Neurological function was assessed and scored (0 = no spontaneous movement of the hindlimbs, 7 = normal gait) at 2, 6, 12 and 24 h (n = 8 at each time point). The animals were then sacrificed and the lumbar segment (L2-5) of the spinal cord was removed for microscopic examination and determination of expression of TLR4 mRNA, NF-κB protein activity and TNF-α and ICAM-1 contents in the spinal cord. Results I/R to the spinal cord significantly increased TLR4 mRNA expression, NF-κB protein activity and TNF-α and ICAM-1 content in the spinal cord and decreased neurological scores in group Ⅱ compared with group C. Simvastatin pretreatment significantly attenuated the I/R-induced increase in the above-mentioned variables and ameliorated I/R-induced neurological dificit and histopathological damage. Conclusion Simvastatin pretreatment has neuroprotective effects on the spinal cord against I/R injury by attenuating inflammatory response.