1.Effect of Bushen Huoxue Granules (补肾活血颗粒) on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice
Qi CHEN ; Peng WANG ; Yingfan CHEN ; Shaodan LI ; Minghui YANG
Journal of Traditional Chinese Medicine 2025;66(4):390-398
ObjectiveTo explore the possible mechanism of action of Bushen Huoxue Granules (补肾活血颗粒, BHG) in the treatment of Parkinson's disease (PD) through the Nrf2/NLRP3 inflammasome axis. MethodsA total of 84 male C57/BL 6 mice were randomly divided into blank group, model group, Madopar group, dimethyl fumarate group, and low-, medium, and high-dose BHG group, with 12 mice in each group. Except for the blank group, all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment, the low-, medium, and high-dose BHG groups were treated with 1.5, 3, and 6 g/(kg·d) of the BHG by gavage, respectively. The Madopar group was given 0.113 g/(kg·d) of Madopar tablets by gavage, and the dimethyl fumarate group was given 50 mg/(kg·d) of dimethyl fumarate solution. The blank group and the model group were given 10 ml/(kg·d) of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test (total distance, central area distance, and average speed), rotarod test (time on the rod), and climbing pole test (climbing time). Serum levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), and myeloperoxidase (MPO) were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein (α-syn) expression. Western Blot was used to detect Nrf2, NLRP3, Caspase-1, and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expression levels of Nrf2, NLRP3, and Caspase-1 in the brain substantia nigra. ResultsCompared with the blank group, the model group showed decreased total distance, central area distance, and average speed, reduced time on the rotarod, prolonged climbing time, reduced TH expression, increased α-syn expression, decreased Nrf2 protein and mRNA expression, increased NLRP3 and Caspase-1 protein and mRNA expression, and elevated serum IL-1β, IL-18, and MPO levels (P<0.05). Compared with the model group, all drug interventions significantly improved the above indicators (P<0.05). There was no significant differences in all indicators between the high-dose BHG group and the Madopar group (P>0.05). Compared with the dimethyl fumarate group, the medium and high-dose BHG groups showed increased Nrf2 mRNA expression in the brain substantia nigra (P<0.05). Compared with the high-dose BHG group, the low-dose group showed decreased total distance, central area distance, and average speed, reduced serum IL-18 levels, decreased α-syn, Nrf2, NLRP3, and Caspase-1 protein levels, and lower Nrf2 mRNA expression (P<0.05). ConclusionThe mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra, thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.
2.Effects of Hewei Anshe Formula (和胃安神方) on the CLOCK and BMAL1 Gene Expression of Hypothalamic Biological Clock in Insomnia Rat Models
Shuo WANG ; Changzhen WANG ; Zhihui LI ; Tianke HUANG ; Liang WANG ; Chujiao TIAN ; Tao ZOU ; Zihan LIU ; Qi CHEN ; Shaodan LI
Journal of Traditional Chinese Medicine 2024;65(20):2145-2151
ObjectiveTo investigate the possible mechanism of Hewei Anshen Formula (和胃安神方) in the treatment of insomnia. MethodsSixty male SD rats were randomly divided into the normal group, the model group, the eszopiclone group and the low-, medium- and high-dose Hewei Anshen Formula groups. The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine (PCPA) for 2 days in all groups except the normal group. After successful modelling, the eszopiclone group was given 0.33 mg/(kg·d) eszopiclone aqueous solution by gavage, the low-, medium- and high-dose Hewei Anshen Formula groups were given 10 ml/kg of Hewei Anshen Formula with a concentration of 1, 2 and 4 g/ml, respectively, and the rats in the normal group and the model group were given 10 ml/kg of saline by gavage, once a day for 7 consecutive days. The general condition of the rats was observed during the experiment, and the body mass of the rats was measured every day after medication administration. The following day after the last medication administration, pentobarbital sodium co-test was used to observe the sleep condition, and the sleep latency and sleep duration were recorded; immunohistochemistry and Western blot were used to detect the expression of hypothalamic clock rhythm regulating protein (CLOCK) and brain and muscle aromatic hydrocarbon receptor nuclear transporter-like protein 1 (BMAL1) in the rats. ResultsThe body mass of rats in the model group was lower than that of rats in the normal group at all time points (P<0.01); compared with the same time in the eszopiclone group, the body mass of rats in the low-dose Hewei Anshen Formula group was elevated on the 5th, 6th and 7th days of medication administration (P<0.05). Compared with the normal group, the sleep duration of rats in the model group was shortened (P<0.01); compared with the model group, the sleep duration of rats in each dosage group increased (P<0.01), and the difference between the high-dose Hewei Anshen Formula group and the eszopiclone group showed no statistically significant (P>0.05), while the sleep duration of the low- and medium-dose Hewei Anshen Formula groups were shorterned than the eszopiclone group (P<0.01). The difference in sleep latency showed no statistically significant among each group (P>0.05). The results of both immunohistochemistry and Western blotting showed that the expression of CLOCK and BMAL1 in the hypothalamus of rats in the model group was significantly reduced compared with that in the normal group (P<0.01); the expression of CLOCK and BMAL1 in the hypothalamus of rats in the low- and high-dose Hewei Anshen Formula groups increased than that in the model group (P<0.05 or P<0.01). ConclusionHewei Anshen Formula can improve insomnia in model rats, and its mechanism of action may be related to the up-regulation of the expression of the hypothalamic biological clock genes CLOCK and BMAL1 protein.
3.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.
4.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.
5.Hewei Anshe Formula (和胃安神方) for Stress-induced Insomnia in Male Patients: A Randomised Controlled Trial of 52 Cases
Chujiao TIAN ; Liang WANG ; Shuo WANG ; Tao ZOU ; Zihan LIU ; Shaodan LI ; Qi CHEN
Journal of Traditional Chinese Medicine 2024;65(22):2326-2331
ObjectiveTo observe the clinical effectiveness and safety of Hewei Anshen Formula (和胃安神方) for stress-induced insomnia. MethodsA total of 104 male patients with stress-induced insomnia were randomly divided into a treatment group and a control group, with 52 cases in each group. The treatment group was given Hewei Anshen Formula once a day, while the control group was given zolpidem tartrate tablets 10 mg per time and once a day, and both groups were treated for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI) was applied to evaluate sleep quality before and after treatment, Ford Insomnia Response to Stress Test (FIRST) was used to evaluate insomnia susceptibility, MOS 36-tem Short Form Health Survey (SF-36) [which includes the domains of Physical Component Summary (PCS) and Mental Health Component Summary (MCS), with the PCS including the General Health (GH), Physical Functioning (PF), Role Physical (RP), and Body Pain (BP), and the MCS including Role Emotional (RE), Social Functioning (SF), Vitality (VT), Mental Health (MH)] was used to evaluate the quality of life, and Fatigue Scale 14 (FS-14) [including somatic fatigue and brain fatigue scores] to evaluate the degree of fatigue, and the traditional Chinese medicine (TCM) syndrome scores using a self-developed TCM syndrome survey for insomnia. Clinical effectiveness and TCM syndrome improvement were determined after treatment. The occurrence of adverse events and adverse reactions was recorded during treatment. ResultsThe total effective rate of clinical effectiveness was 90.38% (41/52) in the treatment group and 80.77% (42/52) in the control group, and the difference between the two groups was not statistically significant (P>0.05). The total effective rate of TCM syndrome effectiveness in the treatment group was 80.77% (42/52), which was higher than 44.23% (23/52) in the control group, and the difference was statistically significant (P<0.01). The TCM syndrome score, FIRST score, brain fatigue scores, brain fatigue score and total score of FS-14 score all reduced after treatment in both groups, and all scores were lower in the treatment group than those in the control group after treatment (P<0.05). All transformed scores of SF-36 scores were higher in both groups after treatment than before treatment in this group, and they were better than the control group in the four dimensions of PF, RP, VT, and MH (P<0.05). There were no adverse events and adverse reactions in the two groups. ConclusionHewei Anshen Formula can improve patients' sleep quality, effectively relieve clinical symptoms such as fatigue and pain, alleviate TCM syndromes, enhance the quality of life, reduce the susceptibility to insomnia, and shows good safety.
6.Procedure and teaching verse of placement of spiral nasoenteral tube into jejunum by gravity-guiding
Pingqing GUO ; Wenqing LIN ; Xiaofeng HUANG ; Congpei LI ; Yanfang DONG ; Lanhua CHEN ; Zhihua CHEN ; Chuanqi CAI ; Xide CHEN ; Qiaoyi WU ; Zhihong LIN ; Shaodan FENG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):92-94
To improve the effectiveness of bedside localization of nasointestinal tube(NIT)and facilitate the placement of nasointestinal tube into jejunum,we established a procedure and composed a teaching verse for bedside placement of nasointestinal tube based on relevant classical literature and our own practices.Verse content:enteral nutrition means a successful strategy to improve the outcome in critically ill patient management,never hesitate to place nasointestinal tubes when necessary.There are several methods to deal with it,but popularizing it remains a long way off.Half-sitting and swallowing into the esophagus,freely withdrawing signifies the stomach cavity.Passing through the pylorus using light tension on the tube in the right lateral decubitus position.Arriving at the jejunum with low resistance in the left lateral decubitus position.What are the signs of intragastric coiling?Tube return out of nose is the initial observation,Failure of air insufflation indicates tube coiling.Dyeing location surpasses imaging.Vacuum test is the most sensitive,Sequential change from acid to base is specific.Methylene blue test is dramatical for localization.Combining three methods is enough to navigate.Abdominal plain film is the goldan standard and can still be used in ultrasonic era.3-D image establishes overall view.CT reveals the tube route exactly.The teaching verse has become a powerful tool for clinical teaching of manual nasointestinal tube placement in a concise and easy-to-remember form.
7.Procedure and teaching verses of supraclavicular subclavian catheterization
Pingqing GUO ; Yilong WU ; Siming LIN ; Lei CHEN ; Congjuan LIN ; Xide CHEN ; Jianqing ZHENG ; Guangwei ZHENG ; Shaodan FENG ; Zhenlyu LIN ; Zhihong LIN
Chinese Critical Care Medicine 2021;33(6):755-756
In order to improve the success rate of supraclavicular deep venous catheterization and reduce mechanical complications, we present an auxillary maneuver in regard to supraclavicular subclavian catheterization basing on the relatively fixed anatomy of subclavian vein and its adjacent surroundings, furthermore, we revised the standardized procedure of supraclavicular subclavian catheterization. The maneuver is summarized in the shape of verses (verses: thumb navigation is well designed according to anatomy. Needle penetrated into vein should be parallel to coronal plane. Fine needle in position should be immobilized. Is it difficult for parallel puncture? Pressure determination is required when needle is in place. It is critical to distinguish which vessel has been inserted. Guidewire is advanced smoothly. Check blood return after expansion of skin and catheterization.). For teaching convenience, verses are considered to be more concise and memorable, as well as applicable to clinical practice, in order to provide some help for clinical teaching.
8.Clinical observation of Shenqi Fuzheng injection combined with chemotherapy for reduction of the side effects of tumor chemotherapy
Fang REN ; Maoyun WANG ; Gege CHEN ; Yixin CUI ; Haiming WANG ; Yu FENG ; Shaodan LI
Cancer Research and Clinic 2018;30(4):251-254
Objective To observe the effect of Shenqi Fuzheng injection combined with chemotherapy on reducing the side effects of malignant tumor chemotherapy. Methods Eighty cancer patients in Traditional Chinese Medicine Hospital of PLA General Hospital from January 2015 to March 2017 were randomly divided into treatment group and control group by using random number table method, each group contained 40 cases. The patients in the treatment group were given Shenqi Fuzheng injection combined with chemotherapy, while the control group used chemotherapy only. Results The incidence of WBC and Plt reduction in the treatment group [35.0 % (14/40), 32.5 % (13/40)] was lower than those in the control group [70.0 % (28/40), 57.5 % (23/40)], and the differences were statistically significant (χ 2= 9.825, P = 0.002;χ2=5.051, P=0.025). The incidence rates of digestive tract reaction and oral ulcers[52.5 %(21/40), 32.5 % (13/40)]were lower than those in the control group[75.0 %(30/40), 60.0 %(24/40)], and the differences were statistically significant (χ2= 4.381, P = 0.036; χ2= 6.084, P = 0.014). The quality of life in the treatment group was significantly improved compared with the control group [(51.4 ±5.1) points vs. (48.3±5.5) points], and the difference was statistically significant(t =2.595,P =0.011). Conclusions Shenqi Fuzheng injection combined with chemotherapy can reduce chemotherapy-induced side effects and improve the life quality of the patients.The injection can be used as the adjuvant therapy for chemotherapy in clinic application.
9.Sepsis associated encephalopathy is an independently risk factor for nosocomial coma in patients with supratentorial intracerebral hemorrhage:a retrospective cohort study of 261 patients
Guangsheng WANG ; Shaodan WANG ; Yeting ZHOU ; Xiaodong CHEN ; Xiaobo MA ; Daoming TONG
Chinese Critical Care Medicine 2016;28(8):723-728
Objective To investigate whether the presence of sepsis associated encephalopathy (SAE) would predict nosocomial coma (NC) and poor outcome in patients with supratentorial intracerebral hemorrhage (SICH). Methods A retrospective cohort study was conducted. The adult acute SICH patients with or without coma admitted to intensive care unit (ICU) of Shuyang People' Hospital Affiliated to Xuzhou Medical University from December 2012 to December 2015 were enrolled. Brain computed tomography (CT) scans were analyzed and the patients were divided into pre-hospital coma (PC) and NC groups. The clinical data and the incidence of SAE of patients in two groups were compared, and the 30-day prognosis was followed up. Univariate and Cox regression analyses were performed to analyze whether SAE would predict NC and poor outcome in patients with SICH. Results A total of 330 patients with acute SICH and coma were enrolled, excluding 60 cases of infratentorial cerebral hemorrhage, 3 cases of primary intraventricular hemorrhage, and 6 cases of unknown volume hematoma. Finally, 261 patients were included, with 111 patients of NC events, and 150 patients of PC events. 69 (62.2%) SAE in SICH with NC and 33 (22.2%) SAE in SICH with PC was diagnosed, and the incidence of SAE between two groups was statistically significant (P < 0.01). Compared with PC group, SICH patients in the NC group had lower incidence of hypertension (81.1% vs. 96.0%), longer time from onset to NC [days: 2.3 (23.9) vs. 0 (0.5)] and length of ICU stay [days: 5.0 (34.0) vs. 3.0 (12.0)], higher initial Glasgow coma score (GCS, 10.2±1.5 vs. 6.6±1.6) and sequential organ failure assessment (SOFA) score [4.0 (6.0) vs. 3.0 (3.0)], lower initial National Institutes of Health Stroke Scale (NIHSS) score (19.4±6.6 vs. 30.2±6.8), as well as more frequent sepsis (78.4% vs. 38.0%), vegetative state (24.3% vs. 14.0%), acute respiratory failure (24.3% vs. 10.0%), pneumonia (37.8% vs. 24.0%), septic shock (8.1% vs. 0), acute liver failure (5.4% vs. 0), hypernatremia (8.1% vs. 0), CT indicating that more frequent vasogenic edema (64.9% vs. 16.0%) and white matter lesion (13.5% vs. 2.0%), and less mannitol usage (94.6% vs. 100.0%), and less brain midline shift (32.4% vs. 68.0%) and hematoma enlargement (8.1% vs. 30.0%), less hematoma volume (mL: 28.0±18.8 vs. 38.3±24.4) in CT, and higher 30-day mortality (54.1% vs. 26.0%) with statistical differences (all P < 0.05). It was shown by Cox regression analyses that SAE [hazard ratio (HR) = 3.5, 95% confidence interval (95%CI) = 1.346-6.765, P = 0.000] and SOFA score (HR = 1.8, 95%CI = 1.073-1.756, P = 0.008) were independent risk factors of death of SICH patients with NC, and hematoma enlargement was independent risk factor of death of SICH patients with PC (HR = 3.0, 95%CI = 1.313-5.814, P = 0.000). Conclusion SAE is the independent factor of inducing NC event and poor prognosis in SICH patients.
10.Diagnosis of sepsis associated encephalopathy:a retrospective analysis of 6 patients
Shaodan WANG ; Guangsheng WANG ; Yeting ZHOU ; Xiaodong CHEN ; Tonghui YANG ; Yantao LIANG ; Daoming TONG
Chinese Journal of Primary Medicine and Pharmacy 2016;23(19):2941-2945
Objective To investigate whether the presence of infection in a case series with coma would predict sepsis associated encephalopathy(SAE).Methods From Jan 2013 to Oct 2014,we used the criteria of systemic inflammatory response syndrome (SIRS)positive sepsis with encephalopathy and retrospective diagnosed a comatose case series with infection and from a tertiary teaching hospital intensive care unit (ICU).Results Among 6 comatose patients with evidence of infection,3 cases were secondary infection after hemorrhagic stroke,1 case was secondary infection after trauma,and the other 2 cases were primary infection.All patients met the diagnosis of SIRS -positive sepsis with encephalopathy.Among them,the presence of SIRS 3 criteria was in 2 cases,four criteria in 4 cases. All patients with severe brain failure (100%),in addition to 5 cases with acute respiratory failure caused by lung injury,one case with acute liver failure.Brain imaging confirmed that the delayed vasogenic edema was in two cases (33.3%),the cerebral ischemic lesions in four cases(66.7%).The ischemic lesion included 1 patient with minor infarcts and 1 case with mild white matter lesions,and with a good prognosis.The other two ischemic cases included multifocal leukoencephalopathy with central pontine myelinolysis in 1 case and extensive white matter lesions in 1 case,eventually with a poor prognosis.Conclusion SAE is a common critically illness,the use of the new classifi-cation criteria of sepsis is helpful in the diagnosis of sepsis associated encephalopathy.

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