1.Improvement effects and mechanism of astragaloside Ⅳ on neuroinflammation
Mimi WANG ; Yonggang FENG ; Yun HAN ; Kaixin SHAN ; Fuyu LIU ; Mingsan MIAO ; Xiaoyan FANG
China Pharmacy 2026;37(1):30-35
OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ (AS- Ⅳ ) on lipopolysaccharide (LPS)-induced neuroinflammation. METHODS BV2 cells were divided into control group, LPS group, AS-Ⅳ groups at concentrations of 20 and 40 μmol/L, and dexamethasone group (2 μmol/L). Except for control group, neuroinflammation model was established with LPS (1 μg/mL) in other groups after medication. The levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO)] in cell supernatant were measured in each group. Mice were randomly divided into normal group, model group, positive control group (Aspirin enteric-coated tablet, 20 mg/kg), AS-Ⅳ low- and high-dose groups (10, 20 mg/kg), with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection, once a day, for 14 consecutive days. Except for normal group, other groups were intraperitoneally injected with LPS (250 μg/kg) 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication; histopathological morphology of cerebral tissue in mice were observed; the co-localization of inducible nitric oxide synthase (iNOS)/ionized calcium binding adapter molecule 1 (Iba1) and CD206/Iba1 in the cerebral cortex region of mice was observed; the expressions of proteins related to the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway in brain tissue of mice were also determined, including NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK). RESULTS In the cell experiments, compared with control group, the levels of IL-6, TNF- α and NO in the cell supernatant of the LPS group were increased significantly (P<0.05); compared with LPS group, the levels of IL-6, TNF-α and NO were decreased significantly in the administration groups (P<0.05). In the animal experiments, compared with the normal group, the serum levels of IL-6 and TNF- α, the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex, and the phosphorylation levels of p38 MAPK, NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group (P<0.05); the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased (P<0.05). The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group, above quantitative indexes of mice were all reversed significantly in administration groups (P<0.05); the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway, promote the M2-type polarization of microglia, and thereby suppress neuroinflammatory responses.
2.Integrative transcriptomic and epigenomic analysis identifies BCL6B as a novel regulator of human pluripotent stem cell to endothelial differentiation.
Yonglin ZHU ; Jinyang LIU ; Jia WANG ; Shuangyuan DING ; Hui QIU ; Xia CHEN ; Jianying GUO ; Peiliang WANG ; Xingwu ZHANG ; Fengzhi ZHANG ; Rujin HUANG ; Fuyu DUAN ; Lin WANG ; Jie NA
Protein & Cell 2025;16(11):985-990
3.Nasolabial groove through the skin flap repair nasal vestibular benign and malignant lesions Application of postoperative tissue defects.
Tongtong GUO ; Sitong GE ; Sijiao SHAN ; Meishan LIU ; Fuyu WANG ; Xian JIANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(3):265-271
Objective:To investigate the application value of nasolabial flaps in addressing tissue defects after resection of benign and malignant nasal vestibular lesions. Methods:The clinical data of patients with benign and malignant nasal vestibular lesions were analyzed retrospectively. There were 4 cases of squamous cell carcinoma, 2 cases of black hairy nevus and 1 case of chronic proliferative inflammatory lesions, all of which were repaired by adjacent nasolabial flap. Results:After 6 months of follow-up, none of the patients developed nasal vestibular contracture or nostril stenosis, and postoperative nasal ventilation function was good. Conclusion:The preoperative design of individual nasolabial flaps is very important for maintaining maxillofacial aesthetics, protectingthe nasolabial framework, and preserving postoperative nasal ventilation function.
Humans
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Retrospective Studies
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Middle Aged
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Nose Neoplasms/surgery*
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Surgical Flaps
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Male
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Female
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Adult
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Nose/surgery*
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Plastic Surgery Procedures/methods*
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Carcinoma, Squamous Cell/surgery*
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Aged
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Skin Transplantation
4.Intrahepatic cholangiocarcinoma tumor size classification based on prognostic analysis: a retrospective multicenter study
Jiaqian CHEN ; Hongzhi LIU ; Lingtian MENG ; Weiping ZHOU ; Zhangjun CHEN ; Jianying LOU ; Shuguo ZHENG ; Xinyu BI ; Jianming WANG ; Wei GUO ; Fuyu LI ; Jian WANG ; Yamin ZHENG ; Jingdong LI ; Shi CHENG
Journal of Surgery Concepts & Practice 2025;30(4):332-338
Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.
5.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
6.Role of spinal cord neuron SAM68-TRPV1 signaling pathway in diabetic neuropathic pain in mice
Hanmin XIANG ; Wanyou HE ; Zhe JIN ; Fuyu WANG ; Hanbing WANG ; Yanlin WANG
Chinese Journal of Anesthesiology 2024;44(5):593-598
Objective:To evaluate the role of spinal cord neuron Src-associated-in-mitosis-68-kDa (SAM68)-transient receptor potential vanilloid-1 channel (TRPV1) signaling pathway in diabetic neuropathic pain (DNP) in mice.Methods:Forty SPF male C57BL/6 mice, aged 8 weeks, weighing 18-22 g, were used in this study. Diabetes mellitus was induced by intraperitoneal streptozotocin 0.12 mg/g, and successful DNP model was defined as decrease in the mechanical paw withdrawal threshold (MWT) of the hind limb≥50% of the baseline value. Twenty-four mice with DNP at 4 weeks after developing the model were divided into 3 groups ( n=8 each) using a simple random sampling: DNP group, SAM68 knocked down group (KD group) and virus control group (VC group). Eight diabetic mice with decrease in MWT <50% were randomly selected as non-DNP group (ND group), and 8 normal mice were randomly selected as control group (NC group). At 4 weeks after developing the diabetes mellitus model, SAM68 gene silencing virus and empty virus were injected into the lumbar enlargement of the spinal cord in KD group and VC group, respectively. MWT was measured before developing the diabetes mellitus model and at 4 and 6 weeks after developing the diabetes mellitus model. The mice were sacrificed after the end of MWT measurement at week 6 after developing the model, spinal cord tissues were collected and the expression of SAM68 and TRPV1 was detected by Western blot, and their localization in the spinal cord was observed by immunofluorescence. Results:Compared with NC and ND groups, the MWT was significantly decreased at 4 and 6 weeks after developing the model, and the expression of SAM68 and TRPV1 in spinal cord tissues was up-regulated in DNP group ( P<0.05). Compared with DNP group, the MWT was significantly increased at 6 weeks after developing the model, the expression of SAM68 and TRPV1 in spinal cord tissues was down-regulated, and no significant change was found in the parameters mentioned above in VC group ( P>0.05). SAM68 and TRPV1 were expressed in neurons in the same region of the spinal cord. Conclusions:Activation of SAM68-TRPV1 signaling pathway in spinal cord neurons is involved in the pathophysiological mechanism of DNP in mice.
7.Role of lactate-induced mitochondrial division of spinal cord neurons in diabetic neuropathic pain in mice
Wenyan PAN ; Jian HE ; Fuyu WANG ; Guanhua LU ; Wanyou HE ; Lei ZHANG ; Chuangqiang ZHANG ; Hanbing WANG
Chinese Journal of Anesthesiology 2024;44(5):603-608
Objective:To evaluate the role of lactate-induced mitochondrial division of spinal cord neurons in diabetic neuropathic pain (DNP) in mice.Methods:Thirty-six SPF-grade healthy adult male C57BL/6 mice, aged 2 months, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (CON group), DNP group, and DNP+ sodium oxalate group (OXA group). The diabetic model was established by intraperitoneal injection of streptozotocin 130 mg/kg. After the diabetic model was successfully established, sodium oxalate 750 mg/kg was intraperitoneally injected once a day for 4 consecutive weeks to inhibit lactate production in OXA group, while the equal volume of normal saline was given instead at the same time in C group and DNP group. The mechanical paw withdrawal threshold (MWT) of the left hindpaw was measured before developing the model and at 1, 2, 3 and 4 weeks after developing the model. After completing the last behavioral testing, the spinal cord tissue of the lumbar segment (L 4-6) was taken for determination of the levels of lactate in serum and spinal cord tissues (by the colorimetric method), expression of the mitochondrial membrane potential, reactive oxygen species (ROS) content (using JC-1 or DHE probes), expression of mitochondrial dynamin-related protein 1 (Drp1) and mitochondrial protein mitofusin 2 (Mfn2) (by Western blot), and co-expression of Drp1 and neuronal neuronal marker neuronal nuclear protein (NeuN) (by immunofluorescence double labeling) and for examination of the structure and the number of mitochondria (with a transmission electron microscope). Results:Compared with C group, the MWT was significantly decreased after developing the model, the levels of lactate in serum and spinal cord tissues and ROS content in the spinal cord were increased, the mitochondrial membrane potential was decreased, the Drp1 expression was up-regulated, the Mfn2 expression was down-regulated, the number of mitochondria was increased, the area was reduced ( P<0.05), and the co-expression of Drp 1 and NeuN was increased in DNP group and OXA group. Compared with DNP group, the MWT was significantly increased after developing the model, the levels of lactate in serum and spinal cord tissues and ROS content in the spinal cord were decreased, the mitochondrial membrane potential was increased, the Drp1 expression was down-regulated, the Mfn2 expression was up-regulated, the number of mitochondria was decreased, the area was increased ( P<0.05), and the co-expression of Drp 1 and NeuN was decreased in OXA group. Conclusions:Lactate-induced excessive mitochondrial division of spinal cord neurons can lead to mitochondrial dysfunction, which may be involved in the maintenance mechanism of DNP in mice.
8.Role of lactate dehydrogenase in diabetic neuropathic pain in mice: relationship with PGC-1α
Fuyu WANG ; Zhe JIN ; Wenyan PAN ; Hanmin XIANG ; Guanhua LU ; Jian HE ; Hanbing WANG ; Yanlin WANG
Chinese Journal of Anesthesiology 2024;44(1):71-75
Objective:To evaluate the role of lactate dehydrogenase in diabetic neuropathic pain (DNP) and the relationship with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in mice.Methods:SPF-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were used to establish diabetes mellitus model by intraperitoneal injection of streptozotocin (STZ) 120 mg/kg. Twenty-four mice with diabetes mellitus were divided into 2 groups ( n=12 each) using a random number table method: DNP group and DNP + oxamate group (OXA group). Another 12 SPF-grade healthy male C57BL/6J mice were selected as control group (C group). In OXA group, oxamate 750 mg/kg was intraperitoneally injected once a day for 28 consecutive days. The equal volume of normal saline was given instead in C group and DNP group. The mechanical paw withdrawal threshold (MWT), blood glucose and body weight were measured at 3 days before STZ injection and at 1, 2, 3 and 4 weeks after STZ injection (T 0-4). After the last behavioural test was completed, blood samples were collected from the posterior orbits of anesthetized mice for determination of serum lactate concentrations. The animals were then sacrificed and the tissues from the prefrontal cortex of the brain were taken for determination of lactate content, mitochondrial membrane potential (by the JC-1), content of reactive oxygen species (ROS) (using dihydroethidium probes), and level of histone lactylation and expression of PGC-1α (by Western blot). Results:Compared with C group, the MWT was significantly decreased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were increased, the mitochondrial membrane potential was decreased, and the expression of PGC-1α was down-regulated in DNP and OXA groups ( P<0.05). Compared with DNP group, no significant change was found in blood glucose and body weight ( P>0.05), the MWT was significantly increased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were decreased, the mitochondrial membrane potential was increased, and the expression of PGC-1α was up-regulated in OXA group ( P<0.05). Conclusions:Lactate dehydrogenase promotes the development of DNP, and the mechanism is related to promotion of increase in histone lactfication and down-regulation of PGC-1α expression in the prefrontal cortex of mice.
9.A multicenter population investigation on precancerous lesions of gastric cancer in Lishui District,Nan-jing
Chunyan NIU ; Xiaoping WANG ; Xiangyang ZHAO ; Jiankang HUANG ; Yue CHEN ; Yongqiang SHI ; Yongqiang SONG ; Hui WANG ; Xinguo WU ; Yongdan BU ; Jijin LI ; Tao TAO ; Jinhua WU ; Changlin XUE ; Fuyu ZHANG ; Jinming YANG ; Chunrong HAN ; Juan YUAN ; Yinling WU ; Hongbing XIONG ; Peng XIAO
The Journal of Practical Medicine 2024;40(20):2929-2934
Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20~29 to 70~79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.
10.Intervention effect of physical exercise on silicotic mice
Fuyu JIN ; Xiaojing WANG ; Wenjing LIU ; Yaqian LI ; Xuemin GAO ; Wenchen CAI ; Na MAO ; Heliang LIU
Journal of Environmental and Occupational Medicine 2023;40(9):997-1004
Background Pneumoconiosis is the most serious occupational disease in China, and silicosis accounts for about half of it. Any intervention effect of physical exercise as the key and core of lung rehabilitation training on silicosis is still unclear. Objective To explore potential intervention effect of physical exercise on silicotic mice. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups, 10 in each group, including a control group, a physical exercise group, a silicosis model group, and a silicosis model + physical exercise intervention group. Silicotic mouse model was established by using 50 μL SiO2 suspension (200 mg·mL−1). A treadmill was used to prepare mice receiving physical exercise at 0° inclination, 12.3 m·min−1, 60 min·d−1, 5 d·week−1 for 4 weeks. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after Van Gieson (VG) staining; expression of p-protein kinase R-like endoplasmic reticulum kinase (PERK) was detected by immunofluorescence staining; expressions of cyclin dependent kinase inhibitors (p21) and p-p38 mitogen activated protein kinase (p38) were detected by immunohistochemistry. The protein expressions of endoplasmic reticulum stress signal factors [p-inositol-requiring enzyme-1α (p-IRE-1α), p-PERK, and p-eukaryotic initiation factor-2α (p-eIF-2α)], senescence signal factors (p-p53, p21, and p16), mitogen-activated protein kinase (MAPK) signal factors [p-p38, p-extracellular regulated protein kinases (p-ERK), and p-stress-activated protein kinase (p-JNK)] were detected by Western blotting. Results After designed acute SiO2 exposure, the images of micro computed tomography (CT) showed high density shadows in lung tissues of the silicotic mice and less shadows in lung tissues of the physical exercise intervention mice. After HE staining, the proportions of silicotic nodule area in lung tissues was (18.67±3.89) % in the silicosis model group, and significantly decreased to (8.78±1.05) % in the silicosis model + physical exercise intervention group (P<0.05). After VG staining, the proportion of collagen fiber area of lung tissues was (10.37±2.18) % in the silicosis model group, and significantly decreased to (4.35±0.89) % in the silicosis model + physical exercise intervention group (P<0.05). The results of immunofluorescence staining showed that in the silicosis model group, the expression of p-PERK increased at the location of silicotic nodules, while in the silicotic model + physical exercise intervention group, the expression of p-PERK decreased. The immunohistochemical staining results showed that the expression of p21 and p-p38 increased in the lung tissues of the silicosis model group; the expression of p21 and p-p38 decreased in the lung tissues of the silicosis model + physical exercise intervention group. The results of Western blotting showed that compared with the control group, the expression levels of p-IRE-1α (0.11±0.03), p-PERK (0.95±0.40), p-eIF-2α (3.53±0.91), p-p53 (1.78±0.07), p21 (1.98±0.10), p16 (1.26±0.17), p-p38 (0.41±0.09), p-ERK (0.42±0.05), and p-JNK (3.20±1.23) of the silicosis model group were all upregulated (P<0.05). Compared with the silicosis model group, the expression levels of p-IRE-1α (0.03±0.01), p-PERK (0.31±0.12), p-eIF-2α (0.30±0.06), p-p53 (0.76±0.08), p21 (0.18±0.11), p16 (0.70±0.24), p-p38 (0.03±0.00), p-ERK (0.19±0.03), and p-JNK (0.46±0.21) of the silicosis model + physical exercise intervention group were downregulated (P<0.05). Conclusion Physical exercise may alleviate pulmonary fibrosis in silicotic mice, and inhibit abnormal expressions of endoplasmic reticulum stress signal, MAPK signal, and senescent signal.

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