1.Effect of Bushen Huoxue Granule (补肾活血颗粒) on Dopamine Homeostasis and ERK/CREB/VMAT2 Signaling Pathways in the Striatum in Parkinson's Disease Model Mice
Hehao SUN ; Yingfan CHEN ; Peng WANG ; Xiaohan GENG ; Yuzhi ZHANG ; Qian ZHANG ; Min LI ; Shaodan LI ; Minghui YANG
Journal of Traditional Chinese Medicine 2025;66(23):2484-2493
ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule (补肾活血颗粒, BHG) in treating Parkinson's disease (PD) from the perspecitve of dopamine (DA) homeostasis. MethodsSeventy-two mice were randomly divided into blank group, model group, madopar group and BHG low-, medium- and high-dose groups, with 12 mice in each group. Except for the blank group, all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to induce a PD model. On the day following the injection, BHG low-, medium- and high-dose groups were administered BHG at doses of 1.25, 2.5, and 5.0 mg/(g·d) by oral gavage, respectively, while the madopar group received madopar tablets at dose of 0.093 8 mg/(g·d) by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test, pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase (TH) in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 (VMAT2) in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB) and VMAT2 in striatum. ResultsCompared to the blank group, mice in the model group showed a significant decline in total distance and average speed in the open field test, along with an increase in total resting time; in the pole test, both the time required for the mice to turn completely downward (T-turn) and the total time taken to reach the bottom of the pole (T-total) were prolonged; forelimb grip strength was reduced; in the striatum, the mean optical density of TH, the average fluorescence intensity of VMAT2 protein, and DA content all decreased, while the number of striatal neurons was reduced, and the DOPAC/DA ratio was elevated; the levels of p-ERK/ERK, p-CREB/CREB, and VMAT2 in the striatum significantly decreased (P<0.01); transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group, mice in the madopar group and BHG low-, medium- and high-dose groups showed significant improvements in all the above indicators (P<0.05 or P<0.01). Compared to madopar group, the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum (P<0.05). Compared to the BHG low-dose group, the BHG high-dose group showed increased total distance and mean velocity, decreased total resting time, T-turn, and T-total, as well as enhanced forelimb grip strength; moreover, the average fluorescence intensity of VMAT2 protein, DA content, p-ERK/ERK, p-CREB/CREB, and VMAT2 levels in the striatum were all significantly elevated (P<0.05 or P<0.01). ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.
2.A multicenter survey on nurses'knowledge and practice of children's sleep management in pediatric ICU
Xiaorui FAN ; Ying GU ; Jing HU ; Shaodan QI ; Linxi HE ; Wenlan ZHANG ; Linjuan WANG ; Weijie SHEN ; Yuxia YANG
Chinese Journal of Nursing 2024;59(4):447-454
Objective To investigate the current status of nurses'knowledge,attitude and practice regarding sleep management of critically ill children in pediatric ICU,and to analyze its impact factors.Methods A self-designed questionnaire on general information and a questionnaire on knowledge and practical behaviors of pediatric ICU nurses on child's sleep management were used.In March 2023,902 pediatric ICU nurses from 24 hospitals in China were surveyed using a convenient sampling method,and the impact factors were analyzed using multiple stepwise linear regression.Results 893 valid questionnaires were collected and the recovery rate of valid questionnaires was 99.00%.Nurses in pediatric ICU scored(33.71±7.76)in knowledge dimension,(37.38±4.86)in attitude dimension and(80.60±16.78)in practice dimension,with a total score of(151.78±24.27).The scores of knowledge and attitude,knowledge and practice,attitude and practice are all positively correlated(r=0.393,P<0.001;r=0.495,P<0.001;r=0.320,P<0.001).The results of multiple stepwise linear regression analysis showed that gender,region,whether they had received sleep management training were the influencing factors of pediatric ICU nurses'total score of knowledge,attitude and practice towards children's sleep management(P<0.05).Conclusion Nurses in pediatric ICU are positive about sleep management for critically ill children,but their knowledge and practice levels need to improve.Nursing managers should strengthen the theoretical knowledge and practical behavioral training of pediatric ICU nurses on child sleep management,develop scientific sleep management plans,and guide nurses to make reasonable evaluation and interventions to improve children's sleep quality.
3.Clinical discussion on the application of invigorating spleen and benefiting qi and controlling blood method for the treatment of cancer therapy-related thrombopenia
Xiang YAN ; Mei LUO ; Jiahui YU ; Yayue ZHANG ; Shaodan TIAN ; Xinyi CHEN ; Menghao LAN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(6):808-812
Cancer therapy-related thrombopenia,which is called"medicinal poison purpura"in tradi-tional Chinese medicine,is a common hematologic adverse reaction during oncology treatment that is dif-ficult to treat due to the differences in oncology treatments and the complexity of the pathogenesis,resul-ting in various degrees of thrombocytopenia.Based on the theory that"spleen controlling blood",this pa-per believes that"medicinal poison purpura"is mainly caused by direct damage to the blood and qi by medicinal poison,leading to qi and blood deficiency;it also attacks the spleen and stomach,resulting in the deficiency of spleen qi and no source of qi and blood production.Due to the spleen deficiency,there is no essence to nourish kidney and bone marrow;their function of generating blood decreases,eventually it becomes"medicinal poison purpura".The theory of"regulating balance and flat regulation"is an im-portant academic idea of our team in the treatment of malignant hematological tumors.In this paper,we have systematically elaborated on the etiology,pathogenesis,and therapeutic principles of the treatment of cancer therapy-related thrombopenia with spleen deficiency pattern through the collation of relevant lit-erature.We believe that the prescription formulated according to the method of invigorating spleen and benefiting qi and controlling blood for the treatment of cancer therapy-associated thrombocytopenia with spleen deficiency pattern is in line with the principle of correspondence between prescription and syn-drome,and correspondence between drugs and syndrome in traditional Chinese medicine,which is theo-retically feasible and has a high clinical application value.
4.Protective Effect of Polysaccharides from Inonotus obliquus on Acute Lung Injury in Mice Based on Gut Microbiota and Metabolomics
Li YU ; Miaoyun YE ; Shaodan CHEN ; Guangjian BAI ; Huinan ZHANG ; Ming YANG ; Yaqi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):86-94
ObjectiveTo explore the protective effect of polysaccharide from Inonotus obliquus (IOP) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MethodA total of 40 male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group, and high-dose and low-dose IOP groups, with eight mice in each group. The high-dose and low-dose IOP groups were administered intragastrically with IOP at 20 and 10 mg·kg-1, respectively. The normal group and the model group were intragastrically administered with normal saline in equal volumes, and the dexamethasone group was intraperitoneally injected with dexamethasone phosphate injection of 30 mg·kg-1 for 21 days. An ALI mouse model induced by LPS was constructed, and hematoxylin-eosin (HE) staining, immunofluorescence staining, and blood routine were used to detect pathological damage of lung tissue and blood cell content. Enzyme-linked immunosorbent assay (ELISA) and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression levels of various inflammatory factors. Changes in gut microbiota and plasma differential metabolites in mice were detected using 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS). ResultCompared with the model group, the lung tissue lesions of ALI mice were significantly improved after IOP administration, and the spleen and thymus index were dramatically increased (P<0.05, P<0.01). The ratio of wet-to-dry weight of lung tissue was sensibly decreased (P<0.05, P<0.01), and the number of lymphocytes was substantially increased (P<0.05, P<0.01). The number of neutrophils was markedly decreased (P<0.01). The expression level of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), nuclear factor-κB(NF-κB), and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) decreased prominently (P<0.05, P<0.01) and the expression level of interleukin-10 (IL-10) increased memorably (P<0.01). The 16S rRNA sequencing results show that IOP can regulate and improve intestinal microbial disorders. The UPLC-Q-TOF-MS results indicate that the treatment of ALI mice with IOP may involve pathways related to mitochondrial, sugar, and amino acid metabolism, such as nucleotide sugar metabolism, histidine metabolism, ubiquinone, and other terpenoid compound-quinone biosynthesis, as well as starch and sucrose metabolism. ConclusionThe improvement of lung tissue lesions and inflammatory response by IOP in ALI mice may be related to maintaining intestinal microbiota balance, regulating mitochondrial electron oxidation respiratory chain, as well as sugar and amino acid metabolism pathways, and affecting the production of related microbial metabolites and tricarboxylic acid cycle metabolites.
5.Clinical Study on the Treatment of Moderate to Severe Stenosing Tenosynovitis of the Flexor Digitorum Tendon with 45° Arc Edge Needle Incision and Traditional Needle Knife Release Surgery
Yingcun MA ; Yingbo MENG ; Xuechang WANG ; Dongzhe ZHANG ; Yali SUN ; Shaodan CHENG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):268-274
Objective To study the safety and effectiveness of arc edge needle therapy for moderate to severe tenosynovitis of the flexor digitorum tendon in the thumb.Methods A total of 62 patients with moderate to severe stenosing tenosynovitis of the flexor digitorum thumb who met the inclusion criteria were collected.The patients were randomly assigned 1:1 to the arc edge needle group and the needle knife group using a random number table method.Among them,31 patients in the arc edge needle group were treated with arc edge needles,while 31 patients in the needle knife group were treated with traditional needle knife release surgery.Both groups were treated once.Record the number rating scale(NRS),range of motion(ROM),Quinell grade,and disease efficacy score(WDES)of patients before and after treatment at various stages(1 week,2 weeks,4 weeks),and at follow-up after 24 weeks to evaluate the treatment effect.Results During the 24 weeks follow-up of 62 patients after treatment,the Quinell grading comparison between the two groups showed that the arc edge needle group was better than the needle knife group(P<0.05);The total effective rate of disease efficacy score(WDES)was 96.77%in the arc edge needle group and 83.87%in the needle knife group.The clinical total effective rate of the arc edge needle group was better than that of the needle knife group(P<0.05);After treatment,both groups showed significant improvement in pain numerical score(NRS)and joint range of motion(ROM),and the degree of improvement increased over time(P<0.05);And the inter group comparison at 1 week,2 weeks,4 weeks and 24 weeks time points after treatment showed that the curved blade needle was superior to the needle knife group in improving pain and joint mobility(P<0.05).Conclusion Both the 45° tenosynovitis incision and release surgery with arc edge needle and traditional needle knife release surgery are effective in treating moderate to severe tenosynovitis of the thumb flexor digitorum tendon.However,the 45° tenosynovitis incision and release surgery with arc edge needle has significant advantages in improving pain,interphalangeal joint mobility,and safety.
6.Construction of a hierarchical comprehensive training system for glaucoma microsurgery
Shaodan ZHANG ; Guoxing LI ; Rongrong LE ; Qi ZHANG ; Yuanbo LIANG
Chinese Journal of Medical Education Research 2024;23(10):1331-1336
Glaucoma is the leading cause of irreversible blindness worldwide. The coverage rate and treatment outcome of glaucoma surgery are crucial for the prevention and treatment of glaucoma-related visual function impairment. This article analyzes the problems and challenges for glaucoma microsurgery training in China and introduces the current status of glaucoma surgery training in China and globally, and based on the experience of cataract surgery training platform in Eye Hospital of Wenzhou Medical University, this article also elaborates on the feasibility of constructing a structured hierarchical comprehensive training system for glaucoma microsurgery, including multimedia theoretical training, Dry-lab, surgical simulator, and a combination of Wet-lab laboratory microsurgery practice and clinical practice, in order to provide a reference for the training of glaucoma sturgeons in China.
7.Inhibitory effect of rapamycin on proliferation, migration and fibrosis of human pterygium fibroblasts in vitro
Di WU ; Xiaonan SUN ; Lin DU ; Xiaoyu ZHANG ; Shanshan LIU ; Jing SUN ; Lin XU ; Shaodan ZHANG
Chinese Journal of Experimental Ophthalmology 2019;36(12):902-907
Objective To investigate the inhibitory effect of rapamycin,an mammalian target of rapamycin (mTOR) pathway inhibitor,on the proliferation,migration and fibrosis of human pterygium fibroblasts (PFBs).Methods Pterygium tissues were collected from patients with primary pterygium who underwent surgical excision in Shenyang Fourth People's Hospital from May to July 2015.The tissues were cultured in vitro and the PFBs were identified by anti-human vimentin immunofluorescence assay.The 3 to 5 generation cells were used for the experiments.The viability of cells treated with different concentrations of rapamycin was detected by methyl thiazolyl tetrazolium (MTT).The cells were divided into normal control group and rapamycin group,and the scratch wound healing test was used to evaluate migration of the PFBs.The expressions of MKI67,α-smooth muscle actin (α-SMA),fibronectin,caspase3,mammalian target of rapamycin (mTOR) and LC3B mRNA were detected by real-time quantitative PCR.Results The cultured cells showed morphology of long spindle and were vimentin immunopositive.The cell viability in rapamycin treated PFBs demonstrated a dose-dependent decrease.At 24 hours after culture,The cell viability in 30 μmol/L rapamycin group was (76.67±8.84)% of that in 0 μmol/L rapamycin group (P<0.001).The relative residual scratch width in 30 μ mol/L rapamycin group was (35.40±11.62) % 48 hours after scratch,which was significantly greater than (2.45±0.76) % in the normal control group (P<0.05).Real-time quantitative PCR showed that the mRNA expressions of MKI67,α-SMA,fibronectin and mTOR in rapamycin group were significantly decreased when compared with those in normal control group (all at P<0.05).The expression of LC3B mRNA in rapamycin group was significantly higher than that in normal control group (P<0.05).The mRNA expression of caspase3 was not significantly different between the two groups (P=0.861).Conclusions Rapamycin can effectively inhibit the proliferation,migration and fibrosis of PFBs without affecting the cell survival.Detailed mechanism remains to be further studied.Rapamycin may serve as an anti-fibrosis agent to prevent the progression and recurrence of pterygium in the future.
8.Inhibitory effect of rapamycin on proliferation,migration and fibrosis of human pterygium fibroblasts in vitro
Di WU ; Xiaonan SUN ; Lin DU ; Xiaoyu ZHANG ; Shanshan LIU ; Jing SUN ; Lin XU ; Shaodan ZHANG
Chinese Journal of Experimental Ophthalmology 2018;36(12):902-907
Objective To investigate the inhibitory effect of rapamycin,an mammalian target of rapamycin (mTOR) pathway inhibitor,on the proliferation,migration and fibrosis of human pterygium fibroblasts (PFBs). Methods Pterygium tissues were collected from patients with primary pterygium who underwent surgical excision in Shenyang Fourth People's Hospital from May to July 2015. The tissues were cultured in vitro and the PFBs were identified by anti.human vimentin immunofluorescence assay. The 3 to 5 generation cells were used for the experiments. The viability of cells treated with different concentrations of rapamycin was detected by methyl thiazolyl tetrazolium ( MTT) . The cells were divided into normal control group and rapamycin group, and the scratch wound healing test was used to evaluate migration of the PFBs. The expressions of MKI67,α.smooth muscle actin (α.SMA), fibronectin,caspase3, mammalian target of rapamycin ( mTOR ) and LC3B mRNA were detected by real.time quantitative PCR. Results The cultured cells showed morphology of long spindle and were vimentin immunopositive. The cell viability in rapamycin treated PFBs demonstrated a dose.dependent decrease. At 24 hours after culture,The cell viability in 30μmol/L rapamycin group was (76. 67±8. 84)% of that in 0μmol/L rapamycin group ( P<0. 001 ) . The relative residual scratch width in 30μmol/L rapamycin group was ( 35. 40 ± 11. 62 )% 48 hours after scratch,which was significantly greater than (2. 45±0. 76)% in the normal control group (P<0. 05). Real.time quantitative PCR showed that the mRNA expressions of MKI67,α.SMA,fibronectin and mTOR in rapamycin group were significantly decreased when compared with those in normal control group (all at P<0. 05). The expression of LC3B mRNA in rapamycin group was significantly higher than that in normal control group (P<0. 05). The mRNA expression of caspase3 was not significantly different between the two groups (P=0. 861). Conclusions Rapamycin can effectively inhibit the proliferation, migration and fibrosis of PFBs without affecting the cell survival. Detailed mechanism remains to be further studied. Rapamycin may serve as an anti.fibrosis agent to prevent the progression and recurrence of pterygium in the future.
9.Conjunctival flora and their antibiotic susceptibility in patients undergoing penetrating intraocular surgeries
Chunyang REN ; Jingna HE ; Lin WANG ; Shanshan LIU ; Jing SUN ; Yong CAO ; Hailin WANG ; Ruoxi LI ; Shaodan ZHANG
Chinese Journal of Experimental Ophthalmology 2018;36(9):704-709
Objective To determine the spectrum of conjunctival flora and the antibiotic susceptibility profiles of patients scheduled for penetrating intraocular surgeries.Methods A prospective case control study was performed.A total of 192 patients (192 eyes) scheduled for penetrating intraocular surgeries at the Fourth People's Hospital of Shenyang from February to August 2015 were enrolled.Samples from the conjunctival sac were collected before instillation of any ophthalmic solutions for both aerobic and anaerobic culture.The positive rate and bacterial spectrum were observed.Bacterial isolates were tested for antibiotic susceptibility to 7 commonly used ophthalmic antibiotics using automated drug resistance analyzing system.The research was approved by the Ethics Committee of the Fourth People's Hospital of Shenyang.Results Totally 91 strains were collected from 81 conjunctival samples during aerobic culture,the positive rate was 42.19%.Staphylococcus epidermidis was the most common microorganism (64.84%),followed by Staphylococcus lentus (7.69%) and Staphylococcus aureus (3.30%).Coagulatase negtive Staphylococcus (CNS) accounted for 80.22% of the positively cultured aerobes.For anaerobic culture,a total of 28 strains were isolated from 28 conjunctival samples,the positive rate was 14.58% Propionibacterium acnes was the predominant species (71.43%),followed by Finegoldia magna (10.71%).Majority of the CNS were sensitive to gentamycin and vancomycin,with resistance rates lower than 10%,but their resistance rate to erythromycin and ceftazidime was 87.67% and 63.01%,respectively.Resistance rate of these CNS to levofloxacin,ciprofloxacin,and moxifloxacin was 42.47%,39.73% and 17.81%,respectively.Multidrug resistance to at least 3 antibiotic classes was present in 38.36% of the CNS.Conclusions Bacteria in the conjunctiva sac of preoperative patients are resistant to various ophthalmic antibiotics.To follow-up the bacterial distribution and antibiotic resistance is great meaningful in the prophylactic and treatment in ocular surgery-related infections.
10.Exploration and application of polyhydroxyalkanoates and polylactic acid membranes during glaucoma filtering surgery and interlaminar transplantation in rabbits
Jichao ZHOU ; Wanwei DAI ; Shaodan ZHANG ; Baohua GUO ; Xinmiao ZENG ; Yalan ZHANG ; Chun ZHANG
Chinese Journal of Comparative Medicine 2018;28(3):36-42
Objective To evaluate the effect of two polymer membranes, polyhydroxyalkanoates(PHA)and polylactic acid(PLA)during glaucoma filtration surgery(GFS),and to evaluate the morphology of membranous PHA after interlamellar implantation. Methods Twenty-eight New Zealand white rabbits were chosen and twenty-four of them were randomly divided into 6 groups(n=4):the PHA-low group,PHA-high group,PLA-low group,PLA-high group,positive control group(MMC group)and blank control group. The rabbits in each group received GFS. The corresponding polymer membranes were implanted under the scleral flap,while the MMC group was treated with 0.2 mg/mL mitomycin C(MMC) for 3 minutes,and the blank control group was treated without extra drugs. The intraocular pressure(IOP)was examined at 0 d,1 d, 3 d, 7 d, 14 d, 28 d and 84 d after GFS. The corneal layers of four rabbits were implanted with PHA membranes and the corneal morphological changes were observed after 84 d. Results The IOP of the PHA-low and PLA-high groups was lower than that of the blank control group at 84 d after GFS(P < 0.05),and was similar with that of the MMC group(P> 0.05). Morphological studies showed that there were no collagenous fibers filling in the duct, and the collagenous fibers around the membranes were generally arranged in parallel. There were no obvious changes in the peripheral collagen structure after implantation of PHA membranes between the corneal layers. Conclusions Application of PHA and PLA membranes during GFS in rabbits may maintain the level of IOP,and the effect is similar with MMC. The mechanism may be achieved through the mechanical blocking of fibrous tissue.

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