1.Research Progress of Vagal Nerve Regulation Mechanism in Acupuncture Treatment of Atrial Fibrillation.
Lu-Lu CAO ; Hui-Rong LIU ; Ya-Jie JI ; Yin-Tao ZHANG ; Bing-Quan WANG ; Xiao-Hong XUE ; Pei WANG ; Zhi-Hui LUO ; Huan-Gan WU
Chinese journal of integrative medicine 2025;31(3):281-288
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology*
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Humans
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Acupuncture Therapy
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Vagus Nerve/physiology*
;
Animals
2.Quercetin Confers Protection against Sepsis-Related Acute Respiratory Distress Syndrome by Suppressing ROS/p38 MAPK Pathway.
Wei-Chao DING ; Juan CHEN ; Quan LI ; Yi REN ; Meng-Meng WANG ; Wei ZHANG ; Xiao-Hang JI ; Xin-Yao WU ; Shi-Nan NIE ; Chang-Bao HUANG ; Zhao-Rui SUN
Chinese journal of integrative medicine 2025;31(11):1011-1020
OBJECTIVE:
To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS).
METHODS:
In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro.
RESULTS:
Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01).
CONCLUSION
Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals
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Sepsis/drug therapy*
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Quercetin/therapeutic use*
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Respiratory Distress Syndrome/enzymology*
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p38 Mitogen-Activated Protein Kinases/metabolism*
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Mice, Inbred C57BL
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Reactive Oxygen Species/metabolism*
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Apoptosis/drug effects*
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Male
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Oxidative Stress/drug effects*
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MAP Kinase Signaling System/drug effects*
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Lung/drug effects*
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Mice
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Lipopolysaccharides
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Macrophages, Alveolar/pathology*
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Inflammation/pathology*
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Protective Agents/therapeutic use*
3.Risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation.
You-Liang HAO ; Fang ZHOU ; Hong-Quan JI ; Yun TIAN ; Zhi-Shan ZHANG ; Yan GUO ; Yang LYU ; Zhong-Wei YANG ; Guo-Jin HOU
China Journal of Orthopaedics and Traumatology 2025;38(2):141-147
OBJECTIVE:
To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation.
METHODS:
A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure.
RESULTS:
There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure.
CONCLUSION
The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans
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Male
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Female
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Hip Fractures/surgery*
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Aged, 80 and over
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Aged
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Risk Factors
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Retrospective Studies
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Fracture Fixation, Intramedullary/adverse effects*
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Bone Nails
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Bone Screws
4.Exploration of Rat Fetal Lung Tissue Fixation Methods
Liyu LIU ; Bo JI ; Xiaoxuan LIU ; Yang FANG ; Ling ZHANG ; Tingting GUO ; Ye QUAN ; Hewen LI ; Yitian LIU
Laboratory Animal and Comparative Medicine 2025;45(4):432-438
ObjectiveThis study explores the methods of lung tissue extraction and fixation required for pathological studies of fetal rats, based on the unique physiological structure of fetal rat lung tissue and existing lung tissue fixation techniques for adult rats. MethodsSix pregnant adult SD rats at 20.5 days of gestation were subjected to cesarean section to obtain fetal rats. Four healthy fetal rats with similar body weight, vital signs, and respiratory status were selected from each pregnant rat, and they were randomly divided into the following groups using a random number table: direct lung infiltration group, lung infiltration group after intratracheal infusion, whole-body infiltration group of fetal rats, and whole-body infiltration group after intratracheal infusion of fetal rats. To systematically compare and analyze the anatomical morphology under different fixation methods, lung tissues from four groups of fetal rats were harvested, perfused, and fixed, and the gross morphology of lung tissues in each group was observed. Paraffin sections were prepared and stained with Hematoxylin-Eosin (H&E). The histological morphology of the whole lung, alveoli, and bronchi was further examined under optical microscopy. ResultsIn the direct lung infiltration group, the hilar structures were unclear, lung lobation was indistinct, the shape was irregular, lung cavities were small, and alveoli and bronchi were shrunken. In the lung infiltration group after intratracheal infusion, the hilar structures were clear, lobation was pronounced, the shape was regular, lung cavities were large, and alveoli and bronchi were full. Both the whole-body infiltration group and whole-body infiltration group after intratracheal infusion of fetal rats exhibited visible lungs, hearts, skins, and other organs. The lung tissues of both groups showed obvious lobulation, irregular shape, and damage at the margins of lung lobes. In the whole-body infiltration group, the thoracic cavities of the fetus were flattened, lung cavities were small, and alveoli and bronchi were shrunken. In the whole-body infiltration group after intratracheal infusion of fetal rats, the fetal thoracic cavities were full, lung cavities were large, and alveoli and bronchi were relatively full. ConclusionThe lung infiltration after intratracheal infusion method for fetal rat lung tissue fixation outperforms direct lung infiltration, whole-body infiltration of fetal rats, and whole-body infiltration after intratracheal infusion of fetal rats in terms of preservation of the lung tissue's original morphology, paraffin sectioning, staining, and pathological observation and analysis. The embedding, sectioning, and staining processes are also simple and save consumables. Therefore, intratracheal infusion followed by lung infiltration method is recommended for fixation in histopathological observation of fetal rat lung tissue.
5.Characteristics of Gut Microbiota Changes and Their Relationship with Infectious Complications During Induction Chemotherapy in AML Patients.
Quan-Lei ZHANG ; Li-Li DONG ; Lin-Lin ZHANG ; Yu-Juan WU ; Meng LI ; Jian BO ; Li-Li WANG ; Yu JING ; Li-Ping DOU ; Dai-Hong LIU ; Zhen-Yang GU ; Chun-Ji GAO
Journal of Experimental Hematology 2025;33(3):738-744
OBJECTIVE:
To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota.
METHODS:
Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications.
RESULTS:
During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143).
CONCLUSION
During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans
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Gastrointestinal Microbiome
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Leukemia, Myeloid, Acute/microbiology*
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Induction Chemotherapy
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Feces/microbiology*
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Male
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Female
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Middle Aged
6.Exploring urban versus rural disparities in atrial fibrillation: prevalence and management trends among elderly Chinese in a screening study.
Wei ZHANG ; Yi CHEN ; Lei-Xiao HU ; Jia-Hui XIA ; Xiao-Fei YE ; Wen-Yuan-Yue WANG ; Xin-Yu WANG ; Quan-Yong XIANG ; Qin TAN ; Xiao-Long WANG ; Xiao-Min YANG ; De-Chao ZHAO ; Xin CHEN ; Yan LI ; Ji-Guang WANG ; FOR THE IMPRESSION INVESTIGATORS AND COORDINATORS
Journal of Geriatric Cardiology 2025;22(2):246-254
BACKGROUND:
Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.
METHODS:
Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics.
RESULTS:
The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05).
CONCLUSIONS
In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.
7.Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.
Quan GAO ; Lin LI ; Qi-Man ZHANG ; Qin-Song SHENG ; Ji-Liang ZHANG ; Li-Jun JIN ; Rui-Yan SHANG
Chinese journal of integrative medicine 2024;30(1):25-33
OBJECTIVE:
To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.
METHODS:
Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.
RESULTS:
The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.
CONCLUSION
Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans
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Proto-Oncogene Proteins c-akt/metabolism*
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Cell Proliferation
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Matrix Metalloproteinase 9
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Molecular Docking Simulation
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Cell Cycle
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ErbB Receptors
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Apoptosis
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Colorectal Neoplasms/pathology*
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Cell Line, Tumor
8.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
9.Establishment of HPLC characteristic chromatogram and quantitative transmission laws for Baqi Rougan Decoction reference sample
Sai-Long GENG ; Qin ZHOU ; Shui-Gen SUN ; Man LI ; Li-Jie ZHAO ; Ji-Quan ZHANG ; Yi FENG
Chinese Traditional Patent Medicine 2024;46(2):370-378
AIM To establish the HPLC characteristic chromatogram of Baqi Rougan Decoction reference sample,and to investigate its quantitative transmission laws.METHODS The contents of calycosin 7-O-glucoside,hesperidin,rosmarinic acid,curcumenol and nystose were determined.The transfer rates of decoction piece-aqueous decoction-reference sample were calculated,after which the paste-forming rate and pH value were recorded.RESULTS There were sixteen characteristic peaks in fifteen batches of reference samples with the similarities of 0.90,nine of which were identified.The average transfer rates of nystose and calycosin 7-O-glucoside in the reference sample were(83.14±6.25)%and(77.81±8.31)%,while those of rosmarinic acid and curcumenol in the aqueous decoction-reference sample were(81.71±6.27)%and(72.16±5.91)%,along with the average paste-forming rate and pH value of(38.91%±1.46%)and 5.13±0.08,respectively.CONCLUSION This stable and feasible method can provide a reference for the selection of preparation process and evaluation of key chemical properties for Baqi Rougan Decoction.
10.Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway
Hai-Zhen DUAN ; Xin ZHOU ; Quan HU ; Meng-Long LIU ; Shu-Hong WANG ; Ji ZHANG ; Xu-Heng JIANG ; Tian-Xi ZHANG ; An-Yong YU
Chinese Journal of Traumatology 2024;27(1):42-52
Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

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