This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective:To observe the changes of macular structure and microvessels in eyes with diabetes macular ischemia (DMI).Methods:A retrospective case study. From January 2023 to July 2023, 23 patients of 31 eyes diagnosed with DMI at Tangshan Ophthalmological Hospital were included in this study. Among them, there were 14 males with 23 eyes; Female cases with 8 eyes. Age were (59.5±4.6) years old. According to the DMI grading standard formulated by the research group for early treatment of diabetes retinopathy, the patients were divided into mild DMI group, moderate DMI group, and severe DMI group, with 8, 12, and 11 eyes respectively. The blood flow density (VD), perfusion area (FA), small vessel VD (SVD), inner retinal capillary plexus VD, FA, and outer retinal, choroidal, and ganglion cell complex (GCC) thickness within 1 mm of the macular fovea in retinal superficial vascular plexus (SVP)were measured using a scanning frequency light source optical coherence tomography instrument. The changes in macular structure and microvasculature in the affected eyes of different degrees of DMI groups were compared and observed. Inter group comparisons were conducted using one-way ANOVA or Kruskal Wallis H-test. Spearman correlation analysis was used to analyze the correlation between DMI severity and GCC, outer retina, choroid thickness, VD, FA and SVP VD, SVD and FA in inner retina. Results:The GCC ( F=70.670), outer retinal thickness ( H=12.393), VD ( F=105.506), SVD ( H=25.300), FA ( F=107.655), and VD ( H=24.098) and FA ( H=25.300) of the retinal SVP in the mild, moderate, and severe DMI groups were compared, and the differences were statistically significant ( P<0.05). There was no statistically significant difference in choroidal thickness ( H=2.441, P>0.05). Pairwise comparison between groups: VD, SVD, FA of GCC thickness and SVP, and VD of inner retina were statistically significant between severe DMI group and moderate DMI group, and between moderate DMI group and mild DMI group ( P<0.05). The thickness of outer retina was statistically significant between severe DMI group and moderate DMI group ( P<0.05). Inner retinal FA: there were statistically significant differences between severe DMI group, moderate DMI group and mild DMI group ( P<0.05). The correlation analysis results showed that GCC ( r s=-0.918), outer retinal thickness ( r s=-0.448), and inner retinal VD ( r s=-0.894) and FA ( r s=-0.918), as well as VD ( r s=-0.919), SVD ( r s=-0.924), and FA ( r s=-0.939) of retinal SVP, were all negatively correlated with the degree of DMI ( P<0.05). There was no correlation between choroidal thickness and degree of DMI ( r s=-0.081, P>0.05). Conclusion:The thickness of GCC, outer retina and choroid, the VD, SVD, and FA of the retinal SVP, the VD and FA of inner retina are all reduced in eyes with different degrees of DMI, while all of them are negatively correlated with the degree of DMI, except for choroid thickness.

Objective:To observe the multimodal imaging characteristics of tamoxifen retinopathy.Methods:A retrospective case study. From January 2019 to December 2021, 4 patients (8 eyes) with tamoxifen retinopathy diagnosed in Tangshan Eye Hospital were included in the study. All patients were female, with sick binoculus. The age was 59.5±4.6 years. After breast cancer resection, tamoxifen 20 mg/d was taken orally consecutively, including 1, 1, and 2 cases who took tamoxifen orally for 5, 7, and ≥10 years. All eyes were examined by fundus color photography, optical coherence tomography (OCT), OCT angiography (OCTA), fundus fluorescein angiography (FFA), and fundus autofluorescence (AF). The multi-mode image features of the fundus of the affected eyes were observed.Results:The yellow white dot crystal like material deposition in the macular area was observed in all eyes. In fundus AF examination, macular area showed patchy strong AF. FFA examination showed telangiectasia and fluorescein leakage in macular area at late stage. OCT showed that punctate strong reflexes could be seen between the neuroepithelial layers in the macular region with the formation of a space between the neuroepithelial layers, the interruption of the elliptical zone (EZ), and the formation of a hole in the outer lamella including 4, 5 and 3 eyes; The thickness of ganglion cells in macular region decreased in 7 eyes. OCTA showed that the blood flow density of the superficial retinal capillary plexus around the arch ring was decreased, and the retinal venules were dilated in 2 eyes; Deep capillary plexus (DCP) showed telangiectasia.Conclusion:Deposition of yellowish white dot like crystals can be seen in the macular region of tamoxifen retinopathy; dotted strong reflex between neuroepithelial layers, cavity formation, thinning of ganglion cell layer, EZ middle fissure and outer lamellar fissure; DCP capillaries and venules around the arch were dilated; telangiectasia in macular region; flaky strong AF in macular region.

BACKGROUND: Nowadays, biological tissue engineering is a growing field of research. Biocompatibility is a key indicator for measuring tissue engineering biomaterials, which is of great significance for the replacement and repair of damaged tissues. METHODS: In this study, using gelatin, carboxymethyl chitosan, and sodium alginate, a tissue engineering material scaffold that can carry cells was successfully prepared. The material was characterized by Fourier transforms infrared spectroscopy. In addition, the prepared scaffolds have physicochemical properties, such as swelling ratio, biodegradability.we observed the biocompatibility of the hydrogel to different adult stem cells (BMSCs and ADSCs) in vivo and in vitro. Adult stem cells were planted on gelatin-carboxymethyl chitosan-sodium alginate (Gel/SA/CMCS) hydrogels for 7 days in vitro, and the survival of stem cells in vitro was observed by live/died staining. Gel/SA/CMCS hydrogels loaded with stem cells were subcutaneously transplanted into nude mice for 14 days of in vivo culture observation. The survival of adult stem cells was observed by staining for stem cell surface markers (CD29, CD90) and Ki67. RESULTS: The scaffolds had a microporous structure with an appropriate pore size (about 80 lm). Live/died staining showed that adult stem cells could stably survive in Gel/SA/CMCS hydrogels for at least 7 days. After 14 days of culture in nude mice, Ki67 staining showed that the stem cells supported by Gel/SA/CMCS hydrogel still had high proliferation activity. CONCLUSION Gel/SA/CMCSs hydrogel has a stable interpenetrating porous structure, suitable swelling performance and degradation rate, can promote and support the survival of adult stem cells in vivo and in vitro, and has good biocompatibility. Therefore, Gel/SA/CMCS hydrogel is a strong candidate for biological tissue engineering materials.

Objective:To investigate the changes of T lymphocyte subsets and cytokines in children with he-patitis B virus(HBV)-associated glomerulonephritis (HBV-GN), and their relationship with HBV-DNA load.Methods:Forty-one children who was the first diagnosed with HBV-GN in Department of Pediatrics, the People′s Hospital of Gansu Province and Institute of Infectious Diseases, the First Hospital of Lanzhou University from September 2012 to September 2016 were collected as the objects(HBV-GN group). At the same time, the 40 patients with HBV infection (chronic HBV infection, normal liver and kidney function, normal 24-hour proteinuria quantitation, no hematuria under the microscope, no recent symptoms of cold and fever, etc.) were enrolled as the control group.The levels of T lymphocyte subset, tumor necrosis factor α(TNF-α), interferon-γ (IFN-γ), interleukin (IL)-2, IL-4, IL-6, IL-8 and IL-10 in the HBV-GN group and the control group were compared, and the relationship between HBV-DNA and cell factors was farther analyzed.Results:Compared with the control group, the proportions of CD3 + T, CD4 + T lymphocyte and CD4 + /CD8 + ratio decreased in the HBV-GN group(0.632±0.052 vs.0.692±0.047, 0.204±0.050 vs.0.466±0.038, 0.006±0.002 vs.0.017±0.003, t=1.025, 3.342, 5.234, all P<0.05), and the proportions of CD8 + T lymphocyte was significantly higher than that in the control group (0.411±0.023 vs.0.220±0.043, t=4.452, P<0.01). Besides, IL-2 and IFN-γ levels in the HBV-GN group were significantly lower than those in the control group[(23.36±2.55) ng/L vs.(36.33±1.24) ng/L, (19.20±2.18) ng/L vs.(61.25±2.08) ng/L, all P<0.05], and the serum levels of TNF-α, IL-4, IL-6, IL-8, and IL-10 were significantly higher than those in the control group[(19.60±1.46) ng/L vs.( 6.68±2.32) ng/L, (13.65±3.34) ng/L vs.(1.35±1.52) ng/L, (5.57±1.02) ng/L vs.(1.43±0.57) ng/L, (26.32±3.45) ng/L vs.(9.68±2.55) ng/L, (19.82±2.78) ng/L vs.(1.02±0.56) ng/L, all P<0.01]. Moreover, in HBV-GN patients, there was negative correlation between HBV-DNA load and IFN-γ, IL-2( r=-0.985, -0.943, all P<0.05), and positive relationship in HBV-DNA load with TNF-α, IL-4, IL-6, IL-8 and IL -10 levels( r=0.942, 0.966, 0.953, 0.944, 0.963, all P<0.05). Conclusions:There is an CD4 + /CD8 + imbalance and an abnormal level of cell factors in HBV-GN progression.In further HBV-GN treatment, HBV-DNA and the cell factors should be detected simultaneously to dynamically eva-luate the illness change and the clinical curative effect.

PURPOSE: Sacral nerve stimulation has been used to treat overactive bladder. This study evaluated the effects of stimulation using different pulse widths on the inhibition of bladder overactivity by sacral nerve stimulation (SNM) in pigs. METHODS: Implant-driven stimulators were used to stimulate the S3 spinal nerve in 7 pigs. Cystometry was performed by infusing normal saline (NS) or acetic acid (AA). SNM at pulse widths of 64 μsec to 624 μsec was conducted at the intensity threshold at which observable perianal and/or tail movement was induced. Multiple cystometrograms were performed to determine the effects of different pulse widths on the micturition reflex. RESULTS: AA-induced bladder overactivity reduced the bladder capacity to 46.9%±7.1% of the NS control level (P<0.05). During AA infusion, SNM at 64 μsec, 204 μsec, and 624 μsec increased the bladder capacity to 126.1%±6.9%, 129.5%±7.3%, and 140.1%±7.6% of the AA control level (P<0.05). No significant differences were found among the results obtained using pulse widths of 64 μsec, 204 μsec, and 624 μsec (P>0.05). The actual intensity threshold varied from 0.7 to 8 V. The mean intensity threshold (T visual) for pulse widths of 64 μs, 204 μs, and 624 μs were 5.64±0.76 V, 3.11±0.48 V, and 2.52±0.49 V. T visual for pulse widths of 64 μsec was larger than the other two T visual for pulse widths of 204 μsec and 624 μsec (P<0.05). No significant differences were found among the T visual for pulse widths of 204 μsec and 624 μsec (P>0.05). CONCLUSIONS: This study indicated that different pulse widths could play a role in inhibiting bladder overactivity. It is not yet certain which pulse widths increased bladder capacity compared with AA levels, to minimize energy consumption and maintain patient comfort during stimulation, 204 μsec may be an appropriate pulse width for SNM.
Acetic Acid ; Humans ; Reflex ; Spinal Nerves ; Swine ; Tail ; Urinary Bladder ; Urinary Bladder, Overactive ; Urination

Objective In order to observe central responses during naturally occurring urinary bladder storage in healthy subjects,we examined brain areas that control strong bladder sensation by resting-state functional magnetic resonance imaging (rs-fMRI).Methods 44 healthy subjects (19 men and 25 women,between 22 and 50 years of age) were screened in the study from October 2014 to October 2016.All subjects were right-handed and scanned twice under the following two conditions:empty bladder (bladder volume ＜ 10 ml)and full bladder (‘strong desire to void’,bladder volume between 200 and 400 ml)without the use of filling with a catheter.Brain imaging softwares (SPM8,DPABI,REST) were adopted to analyze the difference in brain-blood perfusion between these two conditions.Voxel-based analysis of the regional homogeneity (ReHo) was performed to analyze rs-fMRI data including the main excitatory regions and inhibitory areas,peak value (X-axis,Y-axis,Z-axis),clusters size (active volume unit:number of voxel),T value (the excitatory and inhibitory extent of brain active regions).Results The rs-fMRI scans of 44 healthy subjects were analyzed.Nine subjects were excluded because of excessive head movements of more than 1.5 mm and 1.5° in rotation.Data sets were obtained from 35 subjects in two states of bladder,empty bladder and strong desires to void.Increased activity during strong desire to void was observed in the prefrontal cortex (PFC),anterior cingulate cortex (ACC),hypothalamus,temporal lobes and left caudate nucleus.Conclusions There are significant changes in the brain's ReHo during the strong sensation to void.The results suggest that the PFC,the ACC,hypothalamus,temporal lobes and left caudate nucleus play a role in the cerebral control of bladder storage without artificial bladder filling in healthy people.

Objective To evaluate the efficacy of the intravesical injection of botulinum toxin A (BTX-A) and bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).Methods We retrospectively reviewed 153 women with IC/BPS from January 2003 to December 2015.Of the 153 patients,77 were treated with BTX-A(group A),the average age was (56.0 ± 4.1) years old.76 underwent bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation (group B),the average age was (58.0 ± 3.3) years old.The patients were evaluated using the O'Leafy-Saint score,visual analog scale pain score,urinary frequency record and quality of life questionnaire before treatment and 1 week,1,3,6 and 12 months after treatment.Results In group A,only 2 had acute urinary retention,27 received a repeat injection,and 28 were lost to follow-up.In group B,3 had urinary tract infection,15 switched to BTX-A injection at 6 months because the treatment of hydrodistention plus Cystistat instillation is not good.31 were lost to follow-up.BTX-A was shown to remain effective for up to 6 months after treatment.After repeated Chinese BTX-A injections,symptoms improved significantly.Hydrodistention plus Cystistat remained effective for up to 3 months after treatment.Conclusions Intravesical injection of BTX-A is a effective therapeutic option for patients with IC/BPS.The average duration of the effect of one dose of Chinese BTX-A was 6 months.Repeated injection of BTX-A is effective.

Objective To investigate the application effect of group therapy in improving the subjective well-being (SWB) of elderly patients with long-term hospitalization. Methods Totally 100 cases of elderly patients admitted in geriatric ward of Ningbo First Hospital for long-time were selected. Newfoundland scale of happiness (MUNSH) scale and the negative life events questionnaire were used to investigate elderly inpatients, and patients with MUNSH ≤12 points received group therapy. Patients were divided into several groups to receive the intervention according to the negative life events. One year after intervention,patients receiving group therapy were evaluated again by using MUNSH scale to evaluate the intervention effect. Results Among 100 elderly patients,there were 32 cases of high SWB,3 cases of low SWB,and 65 cases of medium SWB. 53 cases of patients had sleep disorders,and 62.26% of them had low SWB. After intervention,the scores of negative experience and emotion of elderly patients were lower than those before intervention (P<0.05);the scores of positive emotion and positive experience and the total MUNSH score were higher than those before intervention (P < 0.05). Conclusions According to the different influencing factors,group interventions can significantly improve the SWB level of elderly patients with long-term hospitalization,so as to improve their quality of life.

Aim To analyze the blocking effect of ( ± ) doxazosin [ ( ± ) DOX ] , ( -) doxazosin [ ( -) DOX] and ( +) doxazosin [( +) DOX] on the vaso-constriction of rat isolated mesenteric arterioles media-ted by α1-adrenoceptors. Methods The vasoconstric-tion induced by phenylephrine ( Phe) in the rat isola-ted mesenteric arterioles ( the second- and third-order branches) was recorded using DMT wire myograph sys-tem 620M, and theα1-adrenoceptor antagonistic activ-ity of ( ± ) DOX and its enantiomers was analyzed. Results The inner diameter of second- and third-or-der branches of the rat mesenteric artery was (162. 5 ± 5. 3) μm (n=11) and (103. 1 ± 2. 3) μm (n=23), respectively. The values of normalized preload of the second-and third-order branches, which were calculat-ed by the LabChart software, were (2. 93 ± 0. 51) mN ( n =11 ) and ( 2. 64 ± 0. 50 ) mN ( n =23 ) ( P >0. 05 ) . Vasoconstrictive responses to Phe in the sec-ond-order branche of rat mesenteric artery under nor-malized preloads were not significantly different from those under 5 mN preload;however, the Emax values of the Phe-induced vasoconstriction under 10 mN, 15 mN and 20 mN preloads were decreased by 12%, 29%and 43% ( P<0. 01 ) respectively compared with those under normalized preload. The concentration-response curves for Phe were shifted to right in a concentration dependent manner by ( -) DOX or ( +) DOX at 0. 001 , 0. 01 and 0. 1 μmol · L-1 without significant change in their Emax values in the second-and third-or-der branches of rat mesenteric artery. Schild plot anal-ysis indicated that ( -) DOX, ( +) DOX and ( ± ) DOX non-competitively inhibited the vasoconstrictive responses to Phe in the second-order branches, and the rank order of pKB values was ( +) DOX ( 8. 67 ± 0. 10 ) , ( ± ) DOX ( 8. 53 ± 0. 090 ) , ( -) DOX (7. 85 ± 0. 09). However, schild plot analysis indica-ted that ( -) DOX and ( +) DOX competitively inhibi-ted the vasoconstrictive responses for Phe in the third-order branch, and the rank order of their pKB values was ( ± ) DOX ( 8. 68 ± 0. 17 ) , ( +) DOX ( 8. 48 ± 0. 10 ) , ( -) DOX ( 7. 48 ± 0. 140 ) . Conclusion The α1-adrenoceptor blocking activity of ( -) DOX is much weaker than that of ( +) DOX or ( ± ) DOX in the rat isolated mesenteric arterioles, and there is a tendency to enhance the activity of ( ± ) DOX in third-order branches of the rat mesenteric artery though theα1-adrenoceptor blockade effect of ( ± ) DOX is not significantly different from ( +) DOX.