1.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
2.Application and research progress of nanotechnology in atherosclerosis
Tingting WANG ; Lili YU ; Xiangli SHEN ; Junmeng ZHENG ; Yushan CHEN ; Shasha SHANG ; Jianru WANG
The Journal of Practical Medicine 2024;40(1):53-58
Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.
3.Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury
Luchun Xu ; Yongdong Yang ; Guozheng Jiang ; Yushan Gao ; Jiawei Song ; Yukun Ma ; Jiaojiao Fan ; Guanlong Wang ; Xing Yu ; Xiangsheng Tang
Journal of Traditional Chinese Medical Sciences 2024;11(4):456-465
Objective:
To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI).
Methods:
An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer.
Results:
From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05).
Conclusion
BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.
4.Visual analysis of molecular and cellular biology of thyroid cancer based on VOSviewer
Peisen DING ; Siyu LIU ; Zhilei XING ; Xiaomeng YU ; Jiahui SONG ; Yushan CUI ; Hongliang LIU
Tianjin Medical Journal 2024;52(9):985-990
Objective To understand the research status and development trend in the field of molecular and cell biology of thyroid cancer.Methods Relevant literature published in the field of molecular and cell biology of thyroid cancer from January 1,2013 to December 31,2022 was obtained in the web of science core collection(WoSCC)according to the search conditions,and bibliometric and visual analysis were performed using the bibliometric software VOSviewer and Excel.Results A total of 1 627 literatures were included.Among them,113 papers were published in 2013,and 214 were published in 2022.The annual number of publications was on the rise.There were 9 274 authors in total,of whom 6 published no less than 10 literatures.There were a total of 2 042 institutions,of which the top 10 institutions were mostly Chinese universities.There were 68 countries in total,and the largest number of publications was China,followed by the United States.There were 513 journals in total,and the top 10 journals with the largest number of literatures were mainly in the field of oncology,followed by the field of endocrinology and metabolism.A total of 62 563 references from 5 887 journals were cited.The most co-cited journal was Journal of Biological Chemistry(1 608 times),and the most co-cited references was Molecular Pathogenesis and Mechanisms of Thyroid Cancer(89 times).Conclusion The field of molecular and cell biology of thyroid cancer is currently developing steadily.Ferroptosis,glycosylation,telomerase reverse transcriptase and oxidative stress are the research frontiers in this field.
5.One case of anti synthetase antibody syndrome characterized by interstitial lung disease
Yushan ZHANG ; Yingying XU ; Zhengfan YU ; Leqiang WANG
Clinical Medicine of China 2024;40(5):375-378
Objective:To strengthen the understanding of clinical features, chest imaging changes and myositis markers of interstitial lung disease associated with anti-synthase syndrome, and to broaden clinical thinking for the diagnosis and treatment of lung disease.Methods:Analyze the clinical diagnosis and treatment process of a patient with anti synthetase antibody syndrome who was admitted to Weifang People's Hospital on March 12, 2023, and summarize the literature.Results:The patient complained of coughing, chest tightness, and shortness of breath for more than 2 months. The initial diagnosis upon admission is community-acquired pneumonia and interstitial pneumonia. After admission, complete relevant auxiliary examinations, supplement the diagnosis of anti synthetase antibody syndrome, and provide standardized treatment Afterwards, the patient's clinical symptoms such as chest tightness and cough were completely relieved, and a follow-up chest CT scan showed a significant reduction in the size of the lesion.Conclusion:For patients with unexplained interstitial pneumonia, it is necessary to actively broaden the diagnosis and treatment thinking, especially considering the possibility of some rheumatic and immune diseases complicated with interstitial lung disease.
6.Dual-responsive nanoparticles with transformable shape and reversible charge for amplified chemo-photodynamic therapy of breast cancer.
Wenfeng JIA ; Rui LIU ; Yushan WANG ; Chuan HU ; Wenqi YU ; Yang ZHOU ; Ling WANG ; Mengjiao ZHANG ; Huile GAO ; Xiang GAO
Acta Pharmaceutica Sinica B 2022;12(8):3354-3366
Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.
7.Effects of electroacupuncture combined with hydrogel on the formation and changes in the glial scar in rats with spinal cord injury
Yang KAITAN ; Gao YUSHAN ; Yang YONGDONG ; Li CHUANHONG ; Cao ZHENG ; Wang XIUMEI ; Li ZAIBO ; Yu XING
Journal of Traditional Chinese Medical Sciences 2022;9(2):197-205
Objective:To observe the effect of electroacupuncture(EA)combined with oriented conductive bio-protein hydrogel(OCBH)on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its effect and mechanism on the formation and changes of glial scars.Methods:A total of 72 female Sprague-Dawley rats were randomly divided into groups according to the treatment received.A rat model of complete SCI was constructed using a spinal cord transection.Behavioral assessments,hematoxylin-eosin(H&E)staining,immunofluorescence staining,and Western blotting were performed at a fixed period after the operation.Results:The material group and the material+EA group obtained better results in the behavioral as-sessments(all P<.05)and the H&E staining.In the immunofluorescence staining and Western blotting,the GFAP protein was expressed more and denser in the material group and the material+EA group than in the model group,and the density of the GFAP expression in the material+EA group was lower at week 12 than in the material group(all P<.05).The expression of complement C3 in the model,material,and material+EA groups decreased in turn.Some inflammatory factors and the NF-kB signaling pathway showed similar results in the Western blotting(all P<.05).The expression of the GDNF protein in the material+EA group was significantly higher than that in the model group and the material group(both P<.01).Conclusion:EA combined with OCBH can promote the recovery of motor functions after SCI by facili-tating the formation of glial scars in the early stage,preventing the further spread of an inflammatory response that would affect the activation of A1/A2 astrocytes and change the morphology of glial scars at the spinal cord-material interface in its late stage.
8.Optimization of the Formulation of Polygala japonica Cream by Central Composite Design-response Surface Methodology Based on AHP-CRITIC Analysis and Its Quality Evaluation
Xue’e LI ; Shu ZHANG ; Hong DENG ; Zhufen LYU ; Yulin TAN ; Jiamin CHEN ; Yushan YU
China Pharmacy 2020;31(21):2615-2621
OBJECTIVE:To optimize the formul ation of Polygala japonica cream,and to evaluate the quality of prepared cream. METHODS :With centrifugal stability ,heat resistance stability and viscosity as evaluation indexes ,the weight coefficient was determined by analytic hierarchy process (AHP),criteria importance through intercriteria correlation (CRITIC)method and mixed weighted AHP-CRITIC ,and the comprehensive score was calculated. The amount of octadecyl alcohol ,hexadecanol and mixed emulsifier (polysorbate 60 mixed with glycerin monostearate at the mass ratio of 2.82)in the formulation of P. japonica cream were screened by central composite design-response surface methodology. The optimized formulation was validated. P. japonica cream prepared by the optimal preparation was evaluated in terms of apperance ,particle,pH,stability and rheological characteristics. RESULTS :The weight coefficients of centrifugal stability ,heat resistance stability and viscosity were 0.428 5, 0.415 6 and 0.155 9 respectively,according to the mixed weighted AHP-CRITIC. The optimal formulations were 1.96 g of hexadecyl alcohol ,5.17 g of octadecyl alcohol ,2.48 g of mixed emulsifier ,1.83 g of polysorbate 60,0.65 g of glyceride monostearate,1 g of benzyl alcohol ,5 g of propylene glycol ,6 g of isopropyl myristate and 5 g of P. japonica extract,and then added water to 100 g. Prepared cream was a light yellow fluid paste with particle size of 0.5-2.5 μm and pH value of 6.5;the results of centrifugal test ,heat resistance test and cold resistance stability test showed that the cream had no oil-water separation or thickened paste. The prepared cream was shear-thinning non-Newtonian fluid. CONCLUSIONS :P. japonica cream is prepared successfully,which shows good apperance ,particle,acidity and stability.
9.Stratified outcomes of "Kidney Disease: Improving Global Outcomes" serum creatinine criteria in critical ill patients: a secondary analysis of a multicenter prospective study
Guiying DONG ; Junping QIN ; Youzhong AN ; Yan KANG ; Xiangyou YU ; Mingyan ZHAO ; Xiaochun MA ; Yuhang AI ; Yuan XU ; Yushan WANG ; Chuanyun QIAN ; Dawei WU ; Renhua SUN ; Shusheng LI ; Zhenjie HU ; Xiangyuan CAO ; Fachun ZHOU ; Li JIANG ; Jiandong LIN ; Erzhen CHEN ; Tiehe QIN ; Zhenyang HE ; Lihua ZHOU ; Bin DU
Chinese Critical Care Medicine 2020;32(3):313-318
Objective:To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.Methods:A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI SCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL·min -1·1.73 m -2, and AoCKD was defined as meeting the KDIGO-AKI SCr standard and baseline eGFR was 15-59 mL·min -1·1.73 m -2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. Results:Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients ( n = 322), AoCKD patients ( n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL·min -1·1.73 m -2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio ( HR) = 4.458, 95% confidence interval (95% CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU ( HR = 5.181, 95% CI was 2.033-13.199, P = 0.001), and AoCKD ( HR = 5.377, 95% CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. Conclusion:Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI SCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.
10.Efficacy of ultraviolet light in influenza B prevention and control in schools of Shenzhen in winter
LI Xuemei, SUN Yushan, XU Zhendong, YU Haihang
Chinese Journal of School Health 2019;40(6):893-895
Objective:
To evaluate the efficacy of ultraviolet light in influenza B prevention and control in schools in Yantian District of Shenzhen in winter, and to provide a reference for preventing and controlling influenza B in schools.
Methods:
Multistage stratified cluster sampling was conducted. Ultraviolet irradiance was detected in 98 classes of 11 schools. The irradiance of different distances under each ultraviolet lamp were measured. Correlational analysis was conducted with influenza cases reported by Shenzhen Student Health Surveillance System.
Results:
A total of 473 ultraviolet lamps were detected, the qualified rate was 53.91%. The effective distance from the lamp corresponding power supply to efficient irradiance was (1.43±0.54)m. The total effective irradiance volume per unit time of each class was(13.65±32.66)m3. Totally 599 influenza cases in 74 classes were reported, with incidence rate of 13.76%. Fifty-eight classes reported influenza clustering, accounting for 59.18%. Average duration of the epidemic was(14.5±25.25)d. Spearman correlation analysis showed that the proportion of irradiance volume per unit time in classroom volume was negatively correlated with class influenza incidence(r=-0.32, P=0.00), but not significant with duration of influenza epidemic(P=0.78). Covariance analysis showed that the incidence of influenza and the duration of influenza epidemic in classes was not significantly correlated with the proportion of irradiance volume per class per unit time in classroom volume (P>0.05).
Conclusion
Ultraviolet light might not effectively reduce the incidence rate of influenza B and the duration of influenza epidemic in schools in Yantian District of Shenzhen over 2017-2018 winter.


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