1.The neuroprotective effect of curcumin by inhibiting the aggregation of α-synuclein on lipopolysaccharide-induced Parkinson's disease model
Xiaokui GAN ; Xiaowei SONG ; Ming ZHANG ; Yiming FANG ; Longbiao MA ; Baosheng HUANG
China Pharmacist 2024;27(5):779-787
Objective To explore the neuroprotective effect of curcumin(Cur)on Parkinson's disease model and its mechanism.Methods Sprague-Dawley rats were randomly divided into the control(CON)group,the model(PD)group,and the low-,medium-,and highdose curcumin(Cur)groups,with ten rats in each group.Lipopolysaccharide was injected into the substantia nigra to establish a Parkinson's disease model.Rats in the Cur groups were administered Cur intraperitoneally at doses of 20 mg/kg,40 mg/kg,and 60 mg/kg daily for 21 days.α-synuclein(α-syn),nuclear transcription factor κB proteins(NF-κB,IKBα,p-NF-κB,p-IKBα)and the activation levels of astrocytes were detected in rat brain tissues by immunohistochemistry(IHC).mRNA levels of pro-inflammatory cytokines(TNF-α,IL-β,IFN-γ,IL-6),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NADPH oxidase complex(gp47phox,gp91phox,gp67phox),and apoptosis-related factors(Bax,Bcl-2,Caspase-3,and Caspase-9)were measured by quantitative reverse transcription polymerase chain reaction(qRT-PCR).The rotarod and pole climbing tests were used to evaluate the motor coordination of the rats.Results Compared to the CON group,PD rats showed significantly increased levels of α-syn,p-NF-κB,p-IKBα proteins,activation of astrocytes,TNF-α,IL-β,IFN-γ,IL-6,iNOS,COX-2,Bax,Caspase-3,Caspase-9,gp47phox,gp91phox and gp67phox mRNA levels(P<0.05);while the Bcl-2 level was significantly decreased(P<0.05).Compared with the PD group,the medium-and high-dose Cur treatment groups inhibited the aggregation of α-syn protein,reduced the activation of the NF-κB pathway,and the expression of inflammatory and apoptosis-related factors(P<0.05).Moreover,medium and high doses of Cur significantly improved the motor coordination in rats,and compared with the PD group,the performance of rotarod and pole climbing tests was significantly improved(P<0.05).Conclusion cur may inhibit the aggregation of α-syn by suppressing neuroinflammation and oxidative stress responses,thereby improving motor coordination in Parkinson's disease rats and exerting neuroprotective effects.
2.Influences of echinacoside on myocardial cell apoptosis and inflammatory injury in rats with coronary heart disease by regulating mTOR/STAT3 signaling pathway
Qiang SU ; Jiahe XIE ; He HUANG ; Shan ZENG ; Yiming ZHONG
Chinese Journal of Immunology 2024;40(12):2574-2579
Objective:To investigate influences of echinacoside(ECH)on myocardial cell apoptosis,inflammatory injury and mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3)signaling pathway in rats with coronary heart disease(CHD).Methods:A total of 12 SD rats were taken as control group(NC group),48 CHD rat models were successfully constructed,and randomly divided into model(Model)group,ECH group(50 mg/kg),mTOR activator MHY1485 group(10 mg/kg),ECH+MHY1485 group(50 mg/kg ECH+10 mg/kg MHY1485).After 4 weeks,electrocardiogram was recorded through biological function experimental system.Kits were used to detect myocardial C-reactive protein(CRP)and IL-6 levels.Myocardial pathology and apoptosis were measured by HE and TUNEL staining.qRT-PCR was used to detect myocardial Bcl-2,Bax mRNA expressions.Western blot was used to detect myocardial mTOR/STAT3 pathway protein expression.Results:Compared with NC group,Model group rats had obvious necrosis,edema and inflammatory cell infiltration,ST segment deviation,IL-6,CRP levels,cardiomyocyte apoptosis rate,Bax mRNA expression,mTOR and p-STAT3/STAT3 protein levels were significantly increased(P<0.05),Bcl-2 mRNA expression was significantly decreased(P<0.05).Compared with Model group,myocardial injury in ECH group was alleviated,ST segment shift,IL-6,CRP levels,cardiomyocyte apoptosis rate,Bax mRNA expression,mTOR and p-STAT3/STAT3 protein levels were were significantly decreased(P<0.05),Bcl-2 mRNA expression was significantly increased(P<0.05).The above indexes of MHY1485 group rats showed opposite trend.MHY1485 eliminates beneficial effects of ECH on CHD rats.Conclusion:ECH may reduce myocardial inflammatory injury and apoptosis in CHD rats by down-regulating mTOR/STAT3 pathway.
3.Predictive value of two-step clustering analysis based on urodynamics for efficacy of sacral neuromodulation in patients with neurogenic bladder
Peixian CHEN ; Hao HUANG ; Qingqing HE ; Yiming LAI ; Weibin XIE ; Fan FAN ; Xiaoxia LI ; Hai HUANG
Chinese Journal of Urology 2024;45(9):686-692
Objective:To perform two-step clustering analysis based on urodynamics in patients with neurogenic bladder (NB) and exploring characteristics affecting success rate of sacral neuromodulation (SNM).Methods:The data of 174 NB patients who received SNM therapy in our hospital from September 2018 to August 2023, were retrospectively analysed. There were 94 males and 80 females, with average age of (50.4±17.9)years, median duration of 2 (1, 3)years, and body mass index of 21.5 (20, 25) kg/m 2. Among them, 50 patients had chronic diseases (hypertension or diabetes). Additionally, 77 patients (44.3%) presented with voiding symptoms, 47 patients (27.0%) with storage symptoms, and 50 patients (28.7%) with mixed symptoms. The etiologies included spinal cord lesions in 110 patients (63.2%), brain lesions in 21 patients (12.1%), peripheral nerve lesions in 36 patients (20.7%), and other causes in 7 patients (4.0%). All patients underwent urodynamics and SNM phase 1 test. If patient's subjective symptoms or objective indicators improved > 50%, it is defined as treatment success and feasible to received second stage of SNM. The success rate was analyzed. Clinical indicators and urodynamic parameter were collected for exploring the difference of the above indicators between two groups (with or without conversion). The 174 patients were grouped using two-step clustering analysis, dividing them into two groups. The differences in clinical data, urodynamic parameters, and the conversion rate of SNM phase II between the two groups were compared. Results:Among these patients, 126 (72%) underwent the second stage of SNM. Compared with the non-conversion group, patients in the conversion group exhibited the following characteristics: high proportion of female[51.6% (65/126) vs. 31.2% (15/48)], younger[(48.1± 18.3)year vs. (56.4±15.4) year], lower proportion of history of chronic disease[23.9% (30/126) vs. 41.7% (20/48)], storage predominant symptoms predominant[33.3% (42/126) vs. 10.4% (5/48)], sensitive bladder sensation[50.0% (63/126) vs. 11.1% (14/48)], normal detrusor contractility [26.2% (33/126) vs. 10.4% (5/48)] and detrusor-sphincter dyssynergia [21.4% (27/126) vs. 4.2% (2/48)]and lower post-void residual [105.5(49.3, 231.3) ml vs. 197.9(114.8, 284.8) ml], ( P<0.05). After excluding multicollinearity, patients were divided into two group mainly based on coordination, detrusor stability, and detrusor contractility through two-step clustering analysis: 98 patients in Group 1 and 76 patients in Group 2. The success rate was higher in Group 2 [82.9% (63/76) vs. 64.3% (63/98), P=0.006]. Compared with Group 1, Group 2 exhibited the following characteristics: higher proportion of storage symptoms [43.4% (33/76) vs. 14.3% (14/98)], sensitive bladder sensation [67.1% (51/76) vs. 26.5% (26/98)], detrusor overactivity [46.1% (35/76) vs. 3.1% (3/98)], normal detrusor contractility [43.4% (33/76) vs. 5.1% (5/98)], and detrusor-sphincter dyssynergia [38.2% (29/76) vs. 0] ( P all<0.05). Additionally, group 2 had lower post-void residual [69.0 (23.8, 136.6) ml and 197.9 (123.2, 287.4) ml] and smaller bladder capacity [(281.9±144.9) ml vs. (430.4±176.7) ml] ( P all<0.01). Conclusions:Patients with storage symptoms, low post-void residual, sensitive bladder sensation, detrusor overactivity, normal contractility, or detrusor-sphincter dyssynergia indicate a higher conversion rate to second stage, making them more suitable for SNM testing.
4.Spag6 Alleviated Brain Edema Injury Caused by Cerebral Ischemia-Reperfusion in Rats by Regulating Motor Cilia Structure and Function
Ruisong HUANG ; Yiming HU ; Pei ZHANG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2024;53(3):295-301,307
Objective To investigate the effect of sperm-associated antigen 6(Spag6)on cerebral edema secondary to ische-mia-reperfusion in rats.Methods Ninety SD rats were randomly assigned to three groups:sham operation group,model group,and experimental group.The rats were treated with lentivirus injection and middle cerebral artery embolization.The infarct vol-ume was evaluated by using 2,3,5-triphenyltetrazolium chloride(TTC)staining.Hematoxylin and eosin(HE)staining was used to observe the damage of ependymal cells and cilia.Scanning electron microscope was used to observe the activity of motile cili-a.Transmission electron microscopy was used to abserve the ultrastructure of nerve cells.The expressions of apoptosis-related proteins Bcl-2,Bax,Survivin,GluN1,GluN2B,and GluA2 were detected using Western blotting.Results After model construc-tion,nerve cells and tissues in different regions of the rat brain were damaged.Spag6 expression,synaptic structure and function were altered.The activity of motor cilia in the third ventricle was disturbed and ischemic cerebral edema was observed.After up-regulation of Spag6 expression,cerebral edema was relieved and the activity of motor cilia was restored.Ischemic cerebral infarc-tion,nerve cell injury and synaptic structural abnormalities were reversed.The protein expression of Bcl-2,Survivin,GluN1,GluN2B,and GluA2 increased significantly(P<0.01 or P<0.05),while the expression of Bax decreased(P<0.01).Conclusion Spag6 enhances synaptic function by restoring the active state of ventricular motor cilia,thereby alleviating ischemic brain edema mediated nerve damage.
5.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.
6.Advances in high-throughput automated organoid-on-a-chip system
Fanlu MENG ; Yiming HAN ; Jidong XIU ; Jianyong HUANG
Tianjin Medical Journal 2024;52(1):1-3
Organoids are in vitro three-dimensional(3D)multicellular cultures that are generated through deploying the self-renewal and self-organizing capacities of stem cells.They recapitulate key structural and functional features of corresponding organs or tissues,providing an ideal in vitro model and research platform for the study of developmental biology,regenerative medicine,disease modeling and drug development.The conventional organoid culture system mainly relies on manual operations with lengthy and complicated procedures,which generate organoid cultures of individual variations and batch differences,limiting their translational applications.Therefore,to engineer the organoid culture system by introducing microfluidic chip technology to enhance the throughput and automation level,is of great significance for achieving large-scale,homogeneous,and standardized organoid cultures.This article reviews the current research progress of high-throughput and automated organoid chips and discusses the main limitations and potential challenges for the future study.
7.Correlation between coronal pressure variation and coronal imbalance in adolescent idiopathic scoliosis patients
Maodong WU ; Qinglun SU ; Yiming HUANG ; Longying SHEN ; Yu LU ; Qin ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(6):852-856
BACKGROUND:The distribution of horizontal pressure in adolescent idiopathic scoliosis can be used to evaluate the coronal imbalance.Currently,there are no reports on the characteristics of coronal pressure distribution and its correlation with coronal imbalance. OBJECTIVE:To explore the correlation between coronal pressure variation and coronal imbalance in adolescent idiopathic scoliosis patients. METHODS:A total of 39 adolescent idiopathic scoliosis patients who met the inclusion and exclusion criteria in Lianyungang First People's Hospital from March 2021 to June 2022 were selected as the adolescent idiopathic scoliosis group,and 30 matched healthy volunteers were recruited from the outpatient department as the control group.The horizontal position pressure,folding position pressure,coefficient of variation,and global and trunk pressure variation were measured by the TBED Postural Couch evaluation system.In the adolescent idiopathic scoliosis group,full-length spine radiographs were taken to measure Cobb angle,coronal balance,apical vertebral deviation and Nash-Moe rotation.The characteristics of coronal pressure variation and its correlation with coronal imbalance were analyzed. RESULTS AND CONCLUSION:(1)Compared with the control group,there was no statistically significant difference in the horizontal position pressure and folding position pressure in the adolescent idiopathic scoliosis group(P>0.05),but the global pressure variation and coefficient of variation were significantly increased(all P<0.05).(2)There were differences in both sides of the trunk of the adolescent idiopathic scoliosis group and the control group(P<0.05),and the convex side pressure variation in the adolescent idiopathic scoliosis group was higher than the concave side pressure variation in the left and right side pressure variation in the control group(all P<0.05).(3)The variation of the convex side pressure of the trunk in adolescent idiopathic scoliosis patients was positively correlated with coronal balance intensity(r=0.692,P<0.05),moderately positively correlated with Cobb angle and apical vertebral deviation(r=0.499,0.595,all P<0.05),and weakly correlated with Nash-Moe grade(r=0.377,P<0.05).The variation of the concave side pressure of the trunk was moderately positively correlated with coronal balance(r=0.410,P<0.05),and the rest was weakly correlated or not correlated(P>0.05).(4)These findings indicate that pressure variation may be used as an adjoint assessment tool in patients with mild to moderate scoliosis.
8.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
9.Chaihu Longgu Mulitang Relieves Generalized Anxiety Disorder in Rats via p38 MAPK/NF-κB Signaling Pathway
Chunxin WEI ; Yiming HU ; Shiqi HUANG ; Guowei TAN ; Yaorong AN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):114-123
ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation, mitigate anxiety-like behavior, and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB (p38 MAPK/NF-κB) signaling pathway in the rat model of generalized anxiety disorder (GAD). MethodTwelve out of 74 Wistar rats were randomly selected as the blank group, and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test (OFT) and elevated Porteus maze test (PMT) were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model, low-, medium-, and high-dose (6, 12, and 24 g·kg-1, respectively) Chaihu Longgu Mulitang, and diazepam (1 mg·kg-1) groups (n=12) and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR)was conducted to determine the mRNA levels of p38 MAPK, NF-κB p65, nuclear factor κB inhibitor α (IκBα), and ionized calcium binding adaptor molecule 1 (Iba-1). The protein levels of p38 MAPK, phosphorylated (p)-p38 MAPK, NF-κB p65, p-NF-κB p65, and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group, the model group had decreased body weight, scattered dark yellow fur, increased irritability, and preference to hibernation in the corner. In addition, the modeled rats showed increased edge movement distance and time in OFT (P<0.01) and decreased movement distance and time and the number of entries in the open arm in PMT (P<0.01). The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus (P<0.01), elevated the levels of IL-1β, IL-6, and TNF-α in the serum and hypothalamus (P<0.01), up-regulated the protein and mRNA levels of p38 MAPK, NF-κB p65, p-p38 MAPK, p-NF-κB p65, and Iba-1 (P<0.05, P<0.01), and down-regulated the protein and mRNA levels of IκBα (P<0.01) in the hypothalamus. Compared with the model group, medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight, improved the fur and behaviors, decreased the edge movement distance and time in OFT (P<0.05, P<0.01), and increased the movement distance and time in the open arm in PMT (P<0.05, P<0.01). Furthermore, they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia (P<0.05, P<0.01), lowered the levels of IL-1β, IL-6, and TNF-α in the serum and hypothalamic tissue (P<0.05, P<0.01), down-regulated the mRNA and protein levels of p38 MAPK, NF-κB p65, p-p38 MAPK, p-NF-κB p65, and Iba-1 (P<0.05, P<0.01), and up-regulated the mRNA and protein levels of IκBα (P<0.05, P<0.01) in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.
10.Research progress on the Copenhagen Psychosocial Questionnaire in the prevention and control of workplace psychosocial hazards
Yiming HUANG ; Min ZHANG ; Chuning HE
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):869-876
Workplace psychosocial hazards may be related to job content or work schedule, specific characteristics of the workplace or opportunities for career development. They can lead to significant losses and harm to workplace relationships, labor participation, productivity and quality within the workplace. This article introduces the definition, types and occupational hazards of workplace psychosocial hazards, as well as the theoretical source, main features and update of the version of the assessment tool Copenhagen Psychosocial Questionnaire, and provides suggestions for the assessment, monitoring, and future scientific research on workplace psychosocial hazards in China.

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