Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.

In order to solve the problems of quality control and traceability of medical test lung for meeting the calibration conditions of JJF 1234-2018 Calibration Specification for Ventilators, the calibration device and method are researched for compliance and airway resistance of medical test lung in this paper. A calibration device for medical test lung is designed using constant volume active piston technology to simulate human breathing. Through comparison experiment, the deviation between this device and the similar foreign device can be found. The deviation is lower than 0.4% for lung compliance and lower than 0.7% for airway resistance. The calibration of lung compliance and airway resistance can be completed by this device. This device has a clear and complete traceability path to ensure quality control from the source. The calibration of ventilator is improved. This paper provides a reference for related metrology departments and medical institutions to study on quality inspection of respiratory medical instruments.
Humans ; Calibration ; Ventilators, Mechanical ; Respiration ; Quality Control ; Lung

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Objective:To investigate the risk of stroke in elderly hypertensive(HTN)patients with varying baseline triglyceride glucose(TYG)index, and to identify the risk factors associated with stroke in this population.Methods:This study was a prospective cohort study that included 459 elderly patients with hypertension who were admitted to Beijing Anzhen Hospital from January 2018 to January 2020.The patients were divided into four groups based on their quartile of TYG index: Q1 group(TYG index≤8.02, 114 cases), Q2 group(8.028.85, 115 cases). The study compared the baseline clinical data and incidence of stroke(hemorrhagic or ischemic stroke)after two years of follow-up among the four groups, and analyzed the risk factors of stroke using Cox regression analyses.Results:This study examined 459 elderly patients with hypertension, of which 251(54.7%)were male and 208(45.3%)were female, with an average age of(71.7 ± 6.2)years(65-79 years). The study found significant differences among the four groups in various factors( P<0.05 for all). The study followed up with patients for a median of 33 months, 55 cases were lost to follow-up.Out of the remaining patients, 10.9% experienced stroke, with 3.7% being hemorrhagic stroke and 7.2% being ischemic stroke.The occurrence of stroke was observed in 5.3%, 8.7%, 13.0%, and 16.2% of patients in the Q1, Q2, Q3, and Q4 groups, respectively.The results of Kaplan-Meier survival analysis demonstrated that the risk of stroke increased gradually as the quartile increased.Specifically, compared to the Q1 group, the risk of stroke increased by 1.016 times(95% CI: 0.933-1.106, P=0.715), 1.264 times(95% CI: 1.067-1.497, P=0.007), and 1.472 times(95% CI: 1.119-1.936, P=0.006)in the Q2, Q3, and Q4 groups, respectively.Notably, both Q3 and Q4 groups showed a significant increase in the risk of ischemic stroke( HR=1.313, 95% CI: 1.016-1.697, P=0.037; HR=1.509, 95% CI: 1.113-2.046, P=0.008), while the Q4 group showed a significant increase in the risk of hemorrhagic stroke( HR=1.132, 95% CI: 1.021-1.255, P=0.019). Multivariate Cox regression analysis showed that male( HR=1.336), smoking history( HR=1.485), hyperlipidemia( HR=1.216), previous stroke( HR=1.547), sleep apnea( HR=1.484), diastolic blood pressure( HR=1.114), hemoglobin( HR=0.962), albumin/creatinine ratio( HR=1.318), low-density lipoprotein cholesterol( HR=1.125), TYG index( HR=1.293), left ventricular mass index( HR=1.103), and anti-platelet therapy( HR=0.874)were all found to be independent risk factors for stroke. Conclusions:In elderly patients with hypertension, there is a significant positive correlation between TYG index and stroke risk, particularly ischemic stroke.This suggests that TYG index could be clinically valuable in improving cerebrovascular risk stratification.

Objective:To investigate the effects of Xiangshao granules on behavior and oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC) of post-stroke depression (PSD) mice.Methods:Eighty C57BL/6 mice were divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, PSD+PBS group, and PSD+Xiangshao group ( n=20). PSD models were constructed using mild chronic unforeseeable stress (CUMS) and solitary feeding after MCAO. MCAO models were evaluated by laser speckle contrast imaging (LSCI), modified neurological severity score (mNSS) and TTC staining. PSD models were evaluated by body mass, sugar and water preference test and tail suspension test. After PSD modeling, mice in the sham-operated group, MCAO group, and PSD+PBS group were given 0.2 mL PBS, while mice in the PSD+Xiangshao group was given Xiangshao granules at dosage of 60 mg/kg (dissolved in 0.2 mL PBS); all were given via intragastric administration once a d for 28 d. Number of OPCs and OLs in mPFC was detected by immunofluorescence. Expressions of myelin basic protein (MBP) and phosphatidylinositol 3-kinase/serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway proteins in mPFC were detected by Western blotting. Results:(1) Model verification results: LSCI showed obvious changes of cerebral blood flow in the middle cerebral artery supply area before, during and after MCAO; TTC staining showed typical red non-infarct area and white infarct area in MCAO group, PSD+PBS group and PSD+ Xiangshao group; mNSS scores in MCAO group, PSD+PBS group and PSD+ Xiangshao group were all >4, without significant differences ( P>0.05); the MCAO model was successfully constructed. After PSD and before treatment, the PSD+PBS group and PSD+Xiangshao group had significantly decreased body weight and sugar-water preference, and statistically prolonged tail suspension immobilization time compared with sham-operated group and MCAO group ( P<0.05); the PSD model was successfully constructed. (2) Results of mouse behavior experiment after treatment: significant differences in body weight, sugar-water preference and tail suspension time were noted in mice of the 4 groups 28 d after treatment ( P<0.05); PSD+Xiangshao group had significantly increased body weight and sugar-water preference and decreased tail suspension immobilization time compared with PSD+PBS group ( P<0.05). (3) Number of OPCs (Olig2 +PDGFRa +), proliferative OPCs (Ki-67 +PDGFRa +, EdU +PDGFRa +) and OLs (Olig2 +CC1 +), and relative MBP, p-PI3K, p-AKT and p-mTOR protein expressions in mPFC of the 4 groups were significantly different ( P<0.05); compared with those in PSD+PBS group, the above cell number and relative protein expressions in PSD+Xiangshao group were significantly increased ( P<0.05). Conclusion:Xiangshao granules can promote the OPCs proliferation and OLs maturation by activating PI3K/AKT/mTOR signaling pathway in mPFC, thus playing a role in PSD.

Objective:To review the incidence and treatment status of perioperative anemia in patients with gastric cancer.Methods:The clinicopathological data of gastric cancer patients who underwent surgery at Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Jan to Dec 2019 were collected. Univariate analysis and multivariate Logistic regression analysis were used to explore the risk factors of preoperative anemia in gastric cancer.Results:A total of 879 patients were included in this study. The incidence of preoperative anemia in patients with gastric cancer was 35.6%. The incidence of postoperative anemia was 63.5%. The proportion of patients with preoperative anemia receiving treatment was 17.3%, and the proportion of patients with postoperative anemia receiving treatment was 17.4%. Univariate analysis showed that age, nutritional risk screening 2002, T stage, M stage, tumor stage and lymph node metastasis were associated with preoperative anemia (all P<0.05). Multivariate Logistic regression analysis showed that age >60 years , nutritional risk screening 2002 ≥3, T 3-4 stage and M 1 stage were independent risk factors for preoperative anemia in patients with gastric cancer (all P<0.05). Conclusions:The incidence of perioperative anemia in patients with gastric cancer is high. At present, the proportion of patients with perioperative anemia receiving treatment is low. High nutritional risk, advanced age, late tumor T stage and distant metastasis are independent risk factors for preoperative anemia in patients with gastric cancer.

Objective:To evaluate the clinical outcomes of additional surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Sixty-nine patients with early gastric cancer who underwent ESD and were diagnosed as having non-curative resection by postoperative pathology at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2020 were included in the retrospective observation. Patients were divided into the additional surgery group ( n=12) and the follow-up group ( n=57). The differences in clinical and pathological data of the two groups, the surgical outcomes of the additional surgery group, three-year recurrence-free survival and tumor-specific survival of the two groups, and the independent risk factors affecting three-year recurrence-free survival in the follow-up group were analyzed. Results:Compared with the follow-up group, the rates of submucosal infiltration [66.7% (8/12) VS 21.1% (12/57), χ 2=7.927, P=0.005], vascular invasion [33.3% (4/12) VS 1.8% (1/57), P=0.003] and nerve invasion [16.7% (2/12) VS 0.0% (0/57), P=0.028] in the additional surgery group were significantly higher. In the additional surgery group, the interval between the additional surgery and ESD was 18.5 d (7-55 d), the surgical time was 286.4±85.9 min, and the number of dissected lymph nodes was 25.6±7.4. Four patients (33.3%) had residual tumor. Postoperative complications occurred in 4 patients (33.3%) (all were discharged after conservative treatment), and there was no perioperative death. One patient developed liver metastases 17 months after the surgery, and died 22 months after surgery due to liver metastases. One patient died 22 months after surgery due to non-tumor causes. The three-year recurrence-free survival and three-year tumor-specific survival in additional surgery group were 91.7% (11/12) and 91.7% (11/12), respectively, and those in the follow-up group were 87.7% (50/57) and 100.0% (57/57), respectively. Multivariate Cox regression analysis showed that tumor size ≥2 cm was an independent risk factor for three-year recurrence-free survival in the follow-up group ( P=0.037, HR=15.595, 95% CI: 1.181-205.952). Conclusion:Additional surgery and close follow-up are safe and feasible therapeutic strategies for early gastric cancer patients who underwent non-curative ESD. Clinicians should make reasonable choice based on the pathological results, patients' physical condition and surgery intention. But for patients with primary tumor size ≥2 cm, additional surgery is recommended.

Objective : To explore the role and molecular mechanism of Supervillin in zebrafish embryo development. Methods : Clustal Omega and DNAman software were used to analyze and compare the homology of amino acid sequences of Svil and SVIL in zebrafish and human. The expression pattern of Svila (subtype of Svil protein in zebrafish) during early embryonic development was analyzed by RT⁃PCR and in situ hybridization. Svila expression in zebrafish was inhibited by injecting morphinos ( MO) , and morphological changes of embryos were observed. The expression and nuclear localization of β ⁃catenin protein were detected by Western blot , and the expression of Wnt/β⁃catenin target gene was detected by RT⁃PCR. Results : During the early embryonic development of zebrafish , Svila was maternally expressed and showed an upward trend with the development process. The expression of Svila was reduced by MO , and the development of zebrafish embryos was distorted and the body axis was bent , which might be related to the blocked movement of concentrated extension of embryos. Further studies showed that Svila expression affected β⁃catenin nuclear transport and Wnt/β⁃catenin signaling pathway activation. Conclusion Svila regulates the concentrated extension movement of zebrafish embryos by activating the Wnt/β⁃catenin signaling pathway.