1.Effect of paeoniflorin regulating PI3K/Akt signaling pathway on inflammatory response in diabetic retinopathy rats
Zhaoliang ZHU ; Shuwei BAI ; Peng DUAN ; Huping SONG ; Tao CHEN
International Eye Science 2025;25(3):365-371
AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.
2.Effect of paeoniflorin regulating PI3K/Akt signaling pathway on inflammatory response in diabetic retinopathy rats
Zhaoliang ZHU ; Shuwei BAI ; Peng DUAN ; Huping SONG ; Tao CHEN
International Eye Science 2025;25(3):365-371
AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.
3.Comparative study of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer
Huanhuan LIU ; Xiaojun ZHANG ; Yue PAN ; Jingfeng ZHANG ; Shuwei SUN ; Jinming ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(6):337-342
Objective:To evaluate the potential of 177Lu-prostate specific membrane antigen (PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and compare it with 177Lu-PSMA-I&T. Methods:177Lu-PSMA-3Q was prepared and the quality control and stability testing were performed. Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were conducted in normal BALB/c mice and 22Rv1 tumor-bearing mice. SPECT imaging was performed on 2 patients (60 and 76 years old) with mCRPC from Chinese PLA General Hospital at 24, 72, and 120 h after injection of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T ((7.40±0.74) GBq). Data were analyzed by using independent-sample t test. Results:177Lu-PSMA-3Q was prepared with the total activity of 74 GBq, the yield rate of 95% (uncorrected), and the radiochemical purity was still above 95% after 168 h at room temperature. The distribution half-lives of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were (0.75±0.22) and (0.86±0.19) min, and the clearance half-lives were (24.74±3.77) and (29.53±3.42) min. Biodistribution of normal mice showed that the uptake values in the liver, lungs, and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177Lu-PSMA-I&T ( t values: 4.24-8.36, all P<0.05). The tumor uptake of 177Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177Lu-PSMA-I&T ((0.856±0.183) vs (0.579±0.126) percentage activity of injection dose per gram of tissue (%ID/g); t=2.78, P=0.024) in 22Rv1 tumor-bearing mice. The rapid clearance pattern resulted in a higher tumor/muscle (T/M) ratio for 177Lu-PSMA-3Q (99.604±11.106), which was significantly higher than that for 177Lu-PSMA-I&T (45.078±10.444; t=7.80, P<0.001). According to SPECT imaging of patients with mCRPC, the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h, with significant difference ( t=7.62, P=0.002). Conclusion:177Lu-PSMA-3Q is easy to label, and has high yield and radiochemical purity, good stability, excellent biological performance, good targeting ability in patients, longer retention time, and fast background clearance rate, which is an ideal prostate cancer treatment drug targeting PSMA.
4.Effect of enriched environment combined with acupuncture at head points on behavior in rats with autism spectrum disorder
Zichen MU ; Qiang TANG ; Yunqiu SHI ; Yan WANG ; Shuwei ZHU ; Ya'nan ZHUANG ; Danshuang XU ; Hongyu LI ; Baolong LI ; Chunyan ZHANG ; Mengke YUAN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(2):176-182
ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.
5.Exosomes derived from mesenchymal stem cells in treatment of animals with acute liver failure:a meta-analysis
Shuwei MA ; Sheng HE ; Bing HAN ; Liaoyun ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(7):1137-1142
OBJECTIVE:To evaluate the efficacy of exosomes derived from mesenchymal stem cells on animal models of acute liver failure. METHODS:PubMed,Web of Science,Embase,The Cochrane Library,CBM,CNKI,WanFang,and VIP databases were retrieved from inception to January 16,2023.A series of animal experiments on the treatment of acute liver failure animal models by exosomes derived from mesenchymal stem cells were collected.Two evaluators screened the literature and extracted the data independently.The bias risk was evaluated by the SYRCLE tool.The extracted data were analyzed by Revmen 5.4.1 software and Stata 17.0 software. RESULTS:A total of 241 articles were retrieved and 9 animal experiments were included,with 219 animals:110 animals in the model group and 109 animals in the exosome group.The results showed that the survival rate of animals in the exosome group improved significantly[RR=9.34,95%CI(3.91,22.29),P<0.001],the levels of serum alanine transaminase[SMD=-5.31,95%CI(-7.43,-3.19),P<0.001]and aspartate aminotransferase[SMD=-4.47,95%CI(-5.85,-3.10),P<0.001]were reduced obviously.The expressions of interleukin-1β[SMD=-11.54,95%CI(-18.12,-4.95),P=0.000 6],interleukin-6[SMD=-5.75,95%CI(-8.08,-3.41),P<0.001]and tumor necrosis factor-α[SMD=-4.46,95%CI(-6.83,-2.09),P=0.000 2],were suppressed obviously. CONCLUSION:Exosomes derived from mesenchymal stem cells effectively inhibit the inflammatory response,ameliorate liver function of animals with acute liver failure,and improve their survival rate.The results of subgroup analysis showed that the shorter survival time of animals(≤24 hours),the lower dose of transplanted exosomes(<1 mg/kg)and the source of exosomes(adipose-derived mesenchymal stem cells)may affect the efficacy of the exosomes derived from mesenchymal stem cells in the animal model of acute liver failure.This conclusion and its clinical transformation still need to be confirmed by randomized controlled studies with large sample sizes and high quality.
6.Research progress of non-coding RNA in methamphetamine-induced addiction and neurotoxicity
Shuwei ZHANG ; Hao CHENG ; Haowei WANG ; Lin MIAO ; Yi LI ; Lina GUAN ; Xiaofeng ZENG
Chinese Journal of Comparative Medicine 2024;34(2):114-121
Methamphetamine(METH)is highly addictive and neurotoxic,which causes cognitive and memory dysfunction in abusers.The harm of METH lies not only in its own toxicity,but also in the high physical and mental dependence of drug addicts,often causing mental disorders and violent behavior,bringing great safety risks to society.Non-coding RNA(ncRNA)does not encode proteins and is an important factor in regulating gene expression at the post-transcriptional level.Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity,but the specific mechanism is unclear.This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity to provide a reference for ncRNA as a forensic identification index and potential therapeutic target for METH abusers.
7.Enhancement Effect of Pre-Treatment 18F-FDG PET/CT Radiomic Features in Prognostic Evaluation of Diffuse Large B-Cell Lymphoma
Xiaolin MENG ; Yue PAN ; Jingjing CUI ; Shuwei SUN ; Hui ZHOU ; Ruimin WANG
Chinese Journal of Medical Imaging 2024;32(3):269-276
Purpose To investigate the predictive value of 18F-FDG PET/CT radiomic features before treatment for progression free survival(PFS)and overall survival(OS)in diffuse large B-cell lymphoma(DLBCL).Materials and Methods A total of 135 patients with pathologically proven DLBCL in Chinese PLA General Hospital from January 2016 to December 2018 and 18F-FDG PET/CT imaging prior to treatment were retrospectively collected.Patients were randomly divided into training set and test set using 8∶2,and then the training set was divided into training set and verification set using 8∶2 to construct the model.Semi-automatically delineated patients'lymphoma lesions as regions of interest and extracted the features.Univariate COX and least absolute shrinkage and selection operator regression were used to screen the features,and the non-zero radiomic features were obtained and the weight coefficients were used to calculate the Radscore value of each patient,and the predictive value of Radscore on PFS and OS was analyzed.Three models were established using traditional prognostic indicators(metabolic parameters and clinical factors),Radscore and combination.C-index,time-dependent area under the curve and decision curve were used to evaluate the model prediction efficiency.Finally,based on the optimal model,a column diagram was drawn,and the calibration curve was used to verify the efficiency of the column diagram.Results The combined model predicted PFS and OS at 3 and 5 years better than the traditional prognostic index model and Radscore model(Z=0.962 1-2.253 9,all P<0.05).Decision curve showed that the combined model achieved the greatest clinical net benefit.The calibration curve showed that the predicted values of the nomogram were in good agreement with the observed values.Conclusion Radscore is an independent prognostic factor for survival in DLBCL patients.The combined model has great application value in guiding the formulation of clinical individualized treatment plan.
8.Research on the effect of different acquisition duration on ROI quantitative parameters in the progress of 18F-FBB PET brain image acquisition
Shina WU ; Meng LIU ; Shuwei SUN ; Yan CHANG ; Jiajin LIU ; Ruimin WANG ; Baixuan XU ; Shulin YAO
China Medical Equipment 2024;21(2):12-15
Objective:To investigate the effect of different acquisition duration of brain image of 18F-florbetaben(18F-FBB)positron emission tomography(PET)on standardized uptake value(SUV).Methods:Eight subjects who underwent 18F-FBB PET examination in Chinese PLA General Hospital from May 2021 to June 2021 were selected,including 5 persons of healthy control and 3 patients with mild cognitive impairment(MCI).All subjects underwent 18F-FBB PET imaging,and the dynamic PET images of them on brains were continuously acquired for 20 min between 90 and 110 min after the 18F-FBB injection was injected as(3.7-5.5 MBq/kg).Under the situation that other reconstruction parameters did not change,the images were reconstructed at 0-1,0-3,0-5,0-10,0-15 and 0-20 min,respectively.The same of region of interest(ROI)ranges were delineated in bilateral frontal cortex,bilateral temporal cortex,bilateral parietal cortex,posterior cingulate gyrus and cerebellar cortex of each group of images.And then,the corresponding mean standardized uptake value(SUVmean)of each region was obtained.The differences of SUVmean values of different ROI values between each group of data images and the images of 0-20 min were compared and analyzed.Results:There were significant differences in SUVmean between the acquired images in 0-1,0-3,0-5 and 0-10 min and the acquired standard images of 0-20 min(t=-7.569--2.410,P<0.05),respectively.There were no significant differences in SUVmean between the acquired images of 0-15 min and the acquired standard images of 0-20 min in the bilateral frontal lobe,bilateral temporal lobe,bilateral parietal cortex and posterior cingulate gyrus(P>0.05),only there was significant difference in the cerebellar cortex area between them(t=-5.597,P<0.001).Conclusion:The results of 15 min can reach to the similar results of 20 min in acquiring images,which can shorten the time of examination,and enhance the degrees of comfort and cooperation of patients in examination.It has clinical application value.
9.Expressions and clinical significances of histone marks H3K9me3 and H3K27me3 in colorectal cancer patients
Yaoqin XUE ; Guojun LIANG ; Yushan ZHAO ; Shuwei WEN ; Laifeng REN
Cancer Research and Clinic 2024;36(2):88-93
Objective:To investigate the expressions and clinical significances of histone marks H3K9me3 and H3K27me3 in colorectal cancer.Methods:A retrospective case-control study was conducted. The clinical data of 98 patients with colorectal cancer in Shanxi Province Cancer Hospital from May 2008 to July 2017 were retrospectively analyzed, including 35 patients in the non-metastatic operation-only group, 29 patients in the synchronous hepatic oligometastasis group and 34 patients in the extensive metastasis group, and 33 patients with benign colorectal lesions who underwent colonoscopy in 2017 were selected as the control group. Immunohistochemical assay was used to detect the expressions of H3K9me3 and H3K27me3 proteins in each group, and the expressions of H3K9me3 and H3K27me3 proteins in colorectal cancer patients with different clinicopathological features were analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed.Results:The positive expression rate of H3K9me3 protein in colorectal cancer group was 11.2% (11/98), which was lower than that in control group [60.6% (22/33)] ( χ2 = 33.33, P < 0.001); the positive expression rate of H3K27me3 protein in colorectal cancer group was 10.6% (13/98), which was lower than that in control group [97.0% (32/33)] ( χ2 = 76.70, P < 0.001). The positive expression rates of H3K9me3 protein were 60.6% (20/33), 17.1% (6/35), 10.3% (3/29) and 5.9 % (2/34) in the control group, the non-metastatic operation-only group, the synchronous hepatic oligometastasis group and the extensive metastasis group, respectively, and the difference was statistically significant ( χ2 = 26.10, P < 0.001); the positive expression rates of H3K27me3 protein were 97.0% (32/33), 14.3% (5/35), 20.7% (6/29) and 5.9% (2/34), respectively, and the difference was statistically significant ( χ2 = 44.16, P < 0.001). The positive expression rate of H3K27me3 in colorectal cancer tissues of patients with lymph node metastasis degree ≤0.2 was higher than that of patients with lymph node metastasis degree >0.2 [22.4% (11/49) vs. 4.2% (2/48), χ2 = 6.98, P = 0.008]. The median overall survival (OS) time of H3K9me3 positive and negative colorectal cancer patients was 77.0 months (95% CI: 10.6-143.3 months) and 34.0 months (95% CI: 25.5-42.5 months), respectively, and there was no significant difference in OS between the two groups ( P = 0.078). The median OS time of H3K27me3 positive and negative colorectal cancer patients was 39.0 months (95% CI: 15.3- 62.7 months) and 34.0 months (95% CI: 24.3-43.7 months), respectively, and there was no significant difference in OS between the two groups ( P = 0.524). Conclusions:The expressions of H3K9me3 and H3K27me3 in colorectal cancer tissues are lower than those in colorectal benign lesions, and gradually decrease with occurrence of liver metastasis and extensive metastasis. H3K9me3 and H3K27me3 may be potential cancer suppressor factors.
10.Vitrectomy combined with intravitreal injection of Dexamethasone sustained-release agent for the treatment of idiopathic macular epiretinal membrane
Shuang WANG ; Shuwei BAI ; Chunling LEI ; Fengzhi LI
International Eye Science 2024;24(10):1624-1628
AIM: To investigate the efficacy of vitrectomy combined with intravitreal injection of dexamethasone sustained-release agent for the treatment of idiopathic macular membrane(IMEM).METHODS: A retrospective analysis was conducted on 72 patients(72 eyes)diagnosed with IMEM at Xi'an People's Hospital from January 2019 to January 2023. They were divided into Group A and Group B according to different treatment method. Group A, consisting of 36 eyes, underwent vitrectomy, epiretinal membrane(ERM)removal surgery, and dexamethasone intraocular injection treatment; group B(36 eyes)only received vitrectomy and ERM removal surgery. Follow up for 12 mo, the best corrected visual acuity(BCVA), intraocular pressure, central macular thickness(CMT), and changes in macular retinal structure before and at 1, 3, 6, and 12 mo after surgery were compared.RESULTS: There were significant differences in BCVA between the two groups at 1, 3, and 6 mo postoperatively(all P<0.05), with group A showing a more significant improvement in visual acuity; there was no significant difference in BCVA between the two groups at 12 mo after surgery(P=0.056). There were significant differences in CMT between the two groups at 1, 3, and 6 mo postoperatively(all P<0.05), with a more significant decrease in CMT of the group A compared with the group B; there was no significant difference in CMT between the two groups at 12 mo after surgery(P=0.165). The comparison of intraocular pressure before and after surgery were all statistically significant(Ftime=2.763, Ptime<0.05; Fintergroup=26.800, Pintergroup<0.05; Finteraction=5.091, Pinteraction<0.05). Group A showed significant structural changes in the macula and retina after surgery.CONCLUSION: Vitreous surgery combined with single intravitreal injection of slow-release dexamethasone in patients with late stage IMEM can rapidly improve macular morphology and help restore visual function within 6 mo after surgery.

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