1.Huaiqihuang Granules Affect Differentiation of Th17 Cells in IgA Vasculitis Nephritis Mice by Regulating AMPK/ACC Pathway
Xinglan YE ; Keying LI ; Jiaxuan LI ; Juan BAI ; Wencheng XU ; Hong LIU ; Xue XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):78-86
ObjectiveTo observe the intervention effect of Huaiqihuang granules (HQH) on immunoglobulin A vasculitis nephritis (IgAVN) mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group, an IgAVN model group, a dexamethasone group (2.5 mg·kg-1·d-1), a low-dose HQH group (4 g·kg-1·d-1), and a high-dose HQH group (8 g·kg-1·d-1). The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling, the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein (24 h UTP), urine β2-microglobulin (β2-MG), serum total protein, albumin, IgA, etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 (Th17) cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α (AMPKα), phosphorylated AMPKα (p-AMPKα), acetyl-CoA carboxylase 1 (ACC1), and phosphorylated ACC1 (p-ACC1) in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group, the IgAVN model group showed significant increases in 24 h UTP, urine β2-MG, total cholesterol (P<0.05), serum interleukin-17 (IL-17), IgA, Th17 proportion in the spleen cell suspension, and IL-17 expression in the spleen tissue (P<0.01), and significantly decreased serum total protein, albumin, p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.01). Compared with the IgAVN model group, in the 4th week, the 24 h UTP, urine β2-MG, serum IL-17, IgA levels, and renal IgA deposition were significantly reduced in each treatment group (P<0.01), and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased (P<0.05, P<0.01). Serum albumin levels significantly increased (P<0.05). Compared with the IgAVN model group, the dexamethasone group and the high-dose HQH group showed increases in serum total protein (P<0.01), p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.05, P<0.01). The high-dose HQH group showed a significant decrease in total cholesterol level (P<0.05). Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway, correcting immune inflammatory disorders, and exerting therapeutic effects on IgAVN.
2.ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy.
Zheng ZHOU ; Keying LI ; Yongchao CHU ; Chao LI ; Tongyu ZHANG ; Peixin LIU ; Tao SUN ; Chen JIANG
Acta Pharmaceutica Sinica B 2023;13(3):1246-1261
As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.
3.Investigation and analysis of smoking behaviour of civil servants in Minhang District, Shanghai
Weiqing GUO ; Keying DING ; Jian WANG ; Hui CHEN ; Jing LUAN ; Zhilian LIU ; Tao LIU ; Jiajie WU ; Qinwen YANG
Journal of Environmental and Occupational Medicine 2022;39(1):47-52
Background The tobacco epidemic as one of the most serious public health problems in the world contributes great harm to human health. It is urgent to develop tobacco control strategy. Civil servants' behaviors as a role model for society have a great influence on the rest of society. Thus, it is important to promote tobacco control program on helping civil servants to quit smoking. Objective To understand the smoking and second-hand smoking exposures status, the awareness of knowledge of tobacco hazards, and the attitudes to tobacco control policies of civil servants in Minhang District, Shanghai. Furthermore, to explore the related strategies and measures for tobacco control, to provide a basis for the development and revision of relevant intervention measures and policies. Methods A total of 20 government agencies with newly installed smoking-free programs from 10 subdistricts and towns in Minhang District, including Xinzhuang, Wujing, Maqiao, Qibao, Meilong, Hongqiao, Zhuanqiao, Jiangchuan, Gumei, and Xinhong were selected as study sites.A questionnaire survey was conducted to investigate all civil servants (n=801) of selected agencies. The questionnaire included general characteristics, smoking and second-hand smoking exposure status, knowledge of tobacco hazard, and attitudes to tobacco control policies. Results A total of 794 civil servants returned valid questionnaires. The awareness rate of tobacco hazards in the smoking group was lower than that in the non-smoking group (P<0.05). Relatively high smoking rates were reported in those being male (17.08%), age ≥51 years old (25.61%), divorced or widowed (12.50%), technical secondary school or below education level (22.81%), having more than 10 years of working years (11.57%), being willing to dissuade indoor smoking (24.54%), having no punishment or warning measures for violation of smoking regulations in workplaces (18.37%), and having no dedicated smoking spot at home (15.38%). The results of multiple logistic regression analysis showed that age 31-40 years old (OR=3.446, 95%CI: 1.236-9.609) and to avoid confronting indoor smoking (OR=3.686, 95%CI: 1.041-13.049) were risk factors for smoking in civil servants. Conclusion Civil servants aged 31-40 years old who deliberately avoid confronting indoor smoking behaviors are the key intervention population of smoking control in Minhang District, Shanghai.
4.Associations between circulating bone-derived hormones osteocalcin, lipocalin 2, and glucose metabolism in patients with acromegaly
Yan ZHANG ; Mengsi LIU ; Keying ZHU ; Wenhuan FENG ; Hong HUANG ; Dalong ZHU ; Ping LI
Chinese Journal of Endocrinology and Metabolism 2020;36(3):246-252
Objective:The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism.Methods:Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables.Results:Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P<0.01] and LCN2 levels decreased [(34.15±9.95 vs 57.50±29.75)ng/ml, P<0.01] in patients with acromegaly. Homeostasis model assessment for insulin resistance (HOMA-IR) was also elevated ( P<0.01), but homeostasis model assessment for β cell function (HOMA-β) and area under curve of insulin during 0-120 min of the oral glucose tolerance test (AUC INS) changed non-significantly in acromegaly compared to normal controls ( P>0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 ( β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin ( β=0.512, P<0.01). In the multivariate models, low LCN2 ( β=-0.398, P=0.017) and elevated serum osteocalcin ( β=0.553, P=0.001) were predictors for AUC INS, osteocalcin was a positive predictor of HOMA- β ( β=0.519, P=0.004). GH ( β=0.294, P=0.029) and IGF-1( β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions:Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly.
5.Research progress in astronaut onboard plyometric training: a review
Keying ZHANG ; Bing ZHANG ; Shujuan LIU ; Zhili LI ; Jianfeng ZHANG ; Minghang GUO
Military Medical Sciences 2017;41(6):534-539
As an effective physical training method to improve the explosive power of athletes, plyometric training(exercise) has made great contributions to the physical training of Chinese Olympic Teams.However,the way this method is used for astronaut onboard training and the maintenance of human body strength is not yet clear enough.There is no training program or system of astronaut onboard training currently available that uses this training method in China.Based on the analysis of related researches at home and abroad, this paper comprehensively and systematically expounds the principles of plyometric training and research related to athletic performance.The view that this method is used for astronaut onboard training is also proposed innovatively in this paper.The aim of this study is to expand the field of physical training for astronauts and provide reference for the training of weightlessness protection in the field of aerospace in China.
6.Metformin inhibits the growth of anaplastic thyroid cancer cell by miRNA/mTOR pathway
Yingying FU ; Guofang CHEN ; Xingjia LI ; Shuhang XU ; Xiaodong MAO ; Chao LIU ; Keying CAI
Chinese Journal of Endocrinology and Metabolism 2017;33(6):506-512
Objective To investigate the effect of metformin on the growth of human anaplastic thyroid cancer cell HTh74Rdox which is doxorubicin resistant. Methods The HTh74Rdox was treated with different concentrations of metformin for 48 h. Cell morphology was observed by microscope, cell viability was tested by methylthiazoletetrazolium (MTT), cell apoptosis by annexin Ⅴ and propidium iodide double staining, the anti-oncogenic miRNA was assayed by realtime fluorescence quantitative PCR (RT-PCR), and the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway tested by western blot. Furthermore, the anti-oncogenic miRNAs were knockdown by miRNA inhibitors (miR-34a, miR-101, miR-125b, and miR-138 inhibitors) and the cells were treated by metformin for 48 h, after that, cell apoptosis was detected by annexin Ⅴ and propidium iodide double staining, the expression of protein related to AMPK/mTOR signaling pathway was detected by western blot. Results Metformin inhibited the growth of human anaplastic thyroid cancer cell HTh74Rdox in a concentration-dependent manner, the cell apoptosis was induced by metformin, and there was a significantly lower expression of miR-34a, miR-101, miR-125b, and miR-138 in the HTh74Rdox. However, the four above miRNAs were upregulated by metformin, and AMPK/mTOR pathway was also activated by metformin. When these miRNAs were suppressed by miR-inhibitors (miR-34a, miR-101, miR-125b, miR-138 inhibitors), the stimulating effect of apoptosis and AMPK/mTOR pathway by metformin were reversed. Conclusion Metformin significantly suppresses cell viability of human anaplastic thyroid cancer cell HTh74Rdox, and stimulates AMPK/mTOR pathway and apoptosis by upregulating the expressions of miR-34a, miR-101, miR-125b, miR-138 in HTh74Rdox cell.
7.Daily calorie restriction and alternate day fasting for type 2 diabetes prevention
Ang ZHENG ; Guofang CHEN ; Keying CAI ; Chao LIU
Chinese Journal of Endocrinology and Metabolism 2016;32(5):433-436
[Summary] Lifestyle intervention is one of the important strategies for the prevention of type 2 diabetes. Recently, caloric restriction regimen has become a hot topic as one of the cornerstone of lifestyle intervention. The alternate day fasting regimen is simple, and increases the patient compliance. Both daily calorie restriction and alternate day fasting regimen can reduce body-weight significantly in pre-diabetes subjects, and reduce the visceral fat mass and the fasting insulin levels, and improve the insulin sensitivity, as well as maintain the lean mass, though the effect on fasting blood glucose was not significant. Nevertheless, the most recent studies have demonstrated that daily calorie restriction,in particular, alternate day fasting regimens can be effective in individuals with pre-diebates in order to prevent type 2 diabetes.
8.Children’s intelligence quotient following general anesthesia for dental care:a clini-cal observation by Chinese Wechsler young children scale of intelligence
Bin XIA ; Jianhong WANG ; Yumeng XIAO ; Keying LIU ; Xudong YANG ; Lihong GE
Journal of Peking University(Health Sciences) 2016;48(2):336-340
Objective:It has been demonstrated that anesthetics exposure may lead to neurocognitive impairment in developing brain of animal models.However,for the limitation that the animal models can-not fully mimic the dose and duration in clinical settings especially for dental general anesthesia,the cli-nical significance of anesthetics exposure on developing central nervous system remains undetermined. Therefore,we conducted the current study in order to observe the fluctuation of intelligence quotient (IQ)after the administration of dental general anesthesia comparing to that before surgery.We conducted the current study in order to observe the fluctuation of intelligence quotient (IQ)after the administration of dental general anesthesia compared with that before surgery.Methods:Thirty two patients,ASA Ⅰ, who were exposed to dental general anesthesia in Department of Pediatric Dentistry Peking University School and Hospital of Stomatology,aged 4 to 6.5 years,were enrolled in this prospective study.Patients with severe learning difficulties or communication disorders were excluded.Written and informed consent was obtained from each patients’family which was fully explained of the purpose and method of study. Their intelligence quotients were evaluated with the Chinese Wechsler young children scale of intelligence (Urban version)before and 2 weeks after dental anesthesia.They were treated by experienced pediatric dentists and the sevoflurane,propofol and nitrous oxide were used for general anesthesia by anesthetist. Articaine hydrochloride and epinephrine tartrate injections were used for their pulp treatment or extrac-tion.The examiners and scorers for IQ had technical training in the test administration.All the patients were tested by the same examiner and with standardized guide language.Each subtest was scored accor-ding to the tool review.Verbal IQ and performance IQ consisted of relevant 5 subtests and full scale IQ. Statistical analyses were performed by SPSS 18.0.All the scores of subtests and 3 types of IQ were ex-pressed as x-±s.Paired two-tailed t test was applied and P<0.05 was accepted as statistically signifi-
cant.Results:The results of intelligent assessment from 28 subjects were collected.The anesthetic time was (163.4 ±32.6)min and the number of treated teeth was 12.1 ±2.3,mean age (4.60 ±0.41 ) years;age range=4.04 to 5.44 years.Among the patients,there were 13 girls and 15 boys.There was no significant difference in gender distribution.The postoperative full IQ (128.46 ±10.85 )was higher than that before surgery (124.64 ±11.46,P=0.017).We found that the elevation of performance IQ, to a large extent,contributed to this change in full IQ (P=0.007).Correspondingly,there was no sta-tistical difference in the verbal IQ,which was 119.68 ±11.74 to 120.21 ±15.61 (P=0.854).Con-clusion:Dental general anesthesia has no negative effect on the intelligence of preschool children,who were treated under general anesthesia by sevoflurane,propofol and nitrous oxide for 2 to 4 hours.The full IQ and performance IQ were slightly enhanced after treatment which can be explained by the memory effect.
9.Replacement therapy of hypothyroidism: Whether the use of levothyroxine is adequate?
Hui ZHU ; Chao LIU ; Keying CAI
Chinese Journal of Endocrinology and Metabolism 2015;31(4):296-299
Hypothyroidism is a common endocrine disease.Its treatment depends on thyroid hormone replacement therapy.Currently,levothyroxine (L-T4) is the preparation recommended by many guidelines.However,there are some L-T4-treated patients with normal TSH levels and persistent non-specific symptoms and discomforts.Therefore,combination therapy with L-T4and liothyronine (L-T3) has been considered as an alternative option for hypothyroidism.However,more prospective studies are needed to provide evidence-based effects for this kind of regimen.
10.Investigation and nursing strategy of illness perceptions in PNE children's parents
Yanyun ZHUANG ; Yanzhao CHEN ; Keying ZHOU ; Liqin YE ; Yanfen LI ; Yalan LIU ; Suping TIAN
Chinese Journal of Modern Nursing 2015;21(13):1504-1507
Objective To investigate illness perceptions of primary nocturnal enuresis(PNE) children's parents,to summarize the nursing countermeasures.Methods A total of 232 children's parents were evaluated using PNE knowledge questionnaire from November 2011 to November 2014.According to the results,children and parents were cared and educated targetly.Then parents were evaluated again after the treatment and nursing intervention.Results A total of 210 parents completed the evaluation,95.2% parents knew PNE was a disease,90.0% parents had correct knowledge of PNE,91.9% parents clearly knew the inducing factors of PNE,91.0% parents clearly knew the detriment of PNE,89.5% parents clearly knew the treatment method of PNE,94.8% parents knew the recovery of PNE.There were significant differences before and after the nursing intervention (x2 =235.347,215.872,207.239,196.039,207.499,216.463,respectively;P < 0.05).Conclusions Newly diagnosed PNE children's parents have a little awareness of the disease,especially lack of the awareness of inducing factors and treatment methods.According to personalcharacter,nursing education can improve the awareness of the disease,and enhance the level of disease control so as to reduce the economic burden on family and society.

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