1.Protective effect and mechanism of Longshengzhi capsules on cerebral ischemia-reperfusion injury in rats
Huanle FANG ; Xiaoming LI ; Yaming ZHOU ; Xin ZHANG ; Xiaoxi LIU ; Yanbin CHEN
China Pharmacy 2024;35(7):813-818
OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion (MCAO) was established by using the improved thread occlusion method. The experiment was divided into six groups: sham surgery group (only separating blood vessels without inserting thread plugs, given the same volume of normal saline), model group (modeling, given the same volume of normal saline), nimodipine group (positive control, modeling, dose of 20 mg/kg), and low-dose, medium-dose, and high-dose groups of Longshengzhi capsules (modeling, doses of 0.72, 1.44 and 2.88 g/kg, respectively), with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage, once a day, for 7 consecutive days. One hour after the last administration, the Zea Longa scoring method was used to score the neurological deficits in each group of rats, and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rats; TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4, NLRP3 and phosphorylated NF-κB (p-NF-κB) protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group, the neural dysfunction score, serum levels of TNF-α and IL-6, cerebral infarction volume ratio, relative expression levels of NF-κB and TLR4 mRNA, as well as protein relative expressions of TLR4, NLRP3 and p-NF-κB in the brain tissue, and relative protein expression of intracellular NF-κB were increased significantly in the model group (P<0.01); the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats, with a large amount of inflammatory cell infiltration; the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group, the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules, as well as the Nimodipine group, were reversed to varying degrees, and most differences were statistically significant (P<0.05 or P<0.01); the pathological morphology observation showed a significant improvement, and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response, thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.
2.Teaching reform and exploration of the graduate biochemistry technology courses based on OBE concept
Ning CHEN ; Xiangfan LIU ; Li LI ; Jiemin WU ; Xiaoxing JIANG ; Qiuli LIANG ; Peihua NI
Chinese Journal of Medical Education Research 2024;23(8):1037-1041
Objective:To investigate the construction effects of the graduate biochemistry technology courses based on the outcome-based education (OBE) concept, analyze the technical needs of graduate students, and further integrate and optimize the teaching methods.Methods:A self-compiled questionnaire with good reliability and validity was used to conduct an overall sampling survey on the graduate students who took the elective courses in Batch 2021 in a medical college in Shanghai. Excel and GraphPad Prism software were used for data analysis.Results:According to this survey, the courses gain good effects in terms of teaching framework, course facilities, teaching forms, teaching contents and comprehensive evaluation of teaching. A total of 112 students (95.2%) thought that the course was very helpful to the expansion of experimental technology and experimental operation ability. However, there were still some teaching needs, such as expanding the types of experiments and increasing experimental operations.Conclusions:Under the guidance of OBE concept, the construction of the graduate biochemistry technology courses has gradually achieved good results. Later, the online-offline hybrid teaching form will be further improved and the curriculum teaching arrangement will be optimized further.
3.Analysis of iodine nutrition monitoring results for key populations in water source high iodine areas of Jiangsu Province in 2020
Mao LIU ; Yunjie YE ; Li SHANG ; Yuting XIA ; Yang WANG ; Peihua WANG
Chinese Journal of Endemiology 2023;42(11):904-907
Objective:To analyze the iodine nutrition status of key populations in water source high iodine areas in Jiangsu Province, providing a reference for scientific prevention and control of water source high iodine hazards.Methods:From May to June 2020, monitoring sites were determined by administrative villages in six high iodine counties (cities, districts) in Jiangsu Province, and drinking water samples were collected from residents to detect the iodine content in the water; 40 non boarding children aged 8 - 10 from one primary school in each village (half male and half female, with an age balance) and 20 pregnant women were selected. Salt samples were taken from children and pregnant women's homes, and urine samples were randomly taken once to detect salt and urine iodine contents. Thyroid volume of children was examined.Results:A total of 36 administrative villages were monitored, with a median of 45.3 μg/L for water iodine, ranging from 8.5 - 372.1 μg/L. A total of 1 422 salt samples were collected, of which 26 were iodized salt, accounting for 1.83%; and 1 396 non iodized salt, with the coverage rate of non iodized salt was 98.17%. A total of 1 365 urine samples were collected from children, with a median urine iodine of 405.6 μg/L. There were statistically significant differences in urine iodine levels among children in different regions, drinking water iodine contents, and age groups ( H = 128.39, 67.81, 39.94, P < 0.001). A total of 57 urine samples were collected from pregnant women, with a median urine iodine of 282.0 μg/L. There were statistically significant differences in urine iodine levels among pregnant women in different regions and drinking water iodine contents groups ( H = 17.54, 18.39, P < 0.001). A total of 1 365 children's thyroid volumes were examined, and 44 cases of thyroid enlargement were detected, with a goiter rate of 3.22%. There were no statistically significant differences in the incidence of thyroid enlargement among children in different regions, drinking water iodine contents, salt types, gender, and age groups ( P > 0.05). Conclusions:The iodine nutrition of children in water source high iodine areas in Jiangsu Province is at an iodine excess level, while the iodine nutrition of pregnant women is at an over optimal level. In areas with high iodine content in water sources, the iodine content in drinking water has a significant impact on the iodine intake of the local population. There is currently no correlation between the iodine content in drinking water, salt type, gender, and age factors and thyroid enlargement in children.
4.Analysis of surveillance results of drinking water-borne endemic fluorosis in Jiangsu Province in 2021
Yunjie YE ; Yuting XIA ; Mao LIU ; Li SHANG ; Peihua WANG ; Yang WANG
Chinese Journal of Endemiology 2023;42(4):320-324
Objective:To learn about the implementation of prevention and control measures in drinking water-borne endemic fluorosis areas and the trend of the disease change in Jiangsu Province.Methods:In March to October 2021, a general survey was carried out in 1 972 villages with drinking water-borne endemic fluorosis in 27 counties (cities and districts) of Jiangsu Province, the operation of water improvement projects in the villages was monitored, and the water fluoride content was determined. The prevalence of dental fluorosis among children aged 8 to 12 years in all the villages was investigated.Results:The 1 972 villages with drinking water-borne endemic fluorosis had completed water improvement, and all water improvement projects were operating normally and the water was qualified. Among them, 1 774 villages in the disease affected areas had achieved the control goal, accounting for 89.96%; and there were 198 villages in the disease affected areas with control measures up to the standard, accounting for 10.04%. A total of 47 water improvement projects were monitored, including 2 small-scale water improvement projects, accounting for 4.26%. There were 45 large-scale water improvement projects, accounting for 95.74%. A total of 125 790 children aged 8 to 12 years were examined, and 12 625 cases of dental fluorosis were detected. The detection rate of dental fluorosis was 10.04%, and the dental fluorosis index was 0.19. The detection rate of dental fluorosis in children aged 8 to 12 years was 9.98% (1 854/18 579), 10.27% (2 704/26 323), 9.48% (2 765/29 152), 9.73% (2 835/29 145) and 10.92% (2 467/22 591), respectively, with statistically significant difference (χ 2 = 10.51, P = 0.015). Among the 198 villages with control measures up to standard, according to the historical water fluoride, the detection rate of dental fluorosis in children in each water fluoride range (1.20-2.00, 2.01-3.00, 3.01-4.00, > 4.00 mg/L) was 37.73% (698/1 850), 43.17% (1 176/2 724), 45.50% (769/1 690) and 55.20% (802/1 453), respectively, with a statistically significant difference (χ 2 = 104.15, P < 0.001). Conclusion:The water improvement measures in drinking water-borne endemic fluorosis areas in Jiangsu Province have achieved significant results, which still need to be further consolidated.
5.Survey results of drinking water iodine level in some areas of Jiangsu Province in 2020
Mao LIU ; Yunjie YE ; Li SHANG ; Yang WANG ; Yuting XIA ; Peihua WANG
Chinese Journal of Endemiology 2023;42(6):473-476
Objective:To dynamically observe the changes in iodine level in residents' drinking water after the change of regional water supply mode (2020) in Jiangsu Province.Methods:The survey of water iodine level was conducted from June to October 2020 in administrative villages of Jiangsu Province with a median water iodine ≥40 μg/L in 2017. The survey mainly covered 1 537 administrative villages in 21 counties (cities and districts) of 5 cities, including Huaian City, Lianyungang City, Suqian City, Yancheng City, and Xuzhou City. Based on the standard of "Definition and Demarcation of Iodine Deficient Areas and Iodine Adequate Areas" (WS/T 669-2020), the administrative villages with a median water iodine of 40 - 100 μg/L were classified as iodine adequate areas. Water iodine testing was conducted using the "Method for Water Iodine Testing in Iodine Deficient and High Iodine Areas" recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:Totally 1 498 administrative villages in Jiangsu Province were monitored in 2020, all of which had centralized water supply. The minimum value of water iodine in all administrative villages was 1.2 μg/L and the maximum value was 606.7 μg/L, and the median water iodine was 35.2 μg/L. Among them, 206 administrative villages had median water iodine < 10 μg/L, accounting for 13.75% (206/1 498); 610 administrative villages had median water iodine from 10 to < 40 μg/L, accounting for 40.72% (610/1 498); 635 administrative villages had median water iodine from 40 to 100 μg/L, accounting for 42.39% (635/1 498); and 47 administrative villages with median water iodine > 100 μg/L, accounting for 3.14% (47/1 498). Except for Sucheng District in Suqian City, Xinyi City and Gulou District in Xuzhou City, Qingjiangpu District and Xuyi County in Huaian City, and Guannan County in Lianyungang City, the median water iodine in the administrative villages of the remaining 15 counties (cities and districts) in 2020 decreased significantly compared to 2017, and the differences were statistically significant ( P < 0.05). Conclusion:After change of regional water supply mode in 2020, in most monitored counties (cities and districts) of Jiangsu Province, the water iodine level of administrative villages has decreased significantly compared to 2017.
6.Construction of evaluation indicator system for health management effects in high-risk stroke population
Miao WEI ; Lina GUO ; Yuanli GUO ; Lü PEIHUA ; Yuru LUO ; Yanjin LIU
Chinese Journal of Health Management 2023;17(10):721-726
Objective:To construct an evaluation indicator system for the health management effects in high-risk stroke population.Methods:From March to May 2020, based on health ecology theory, social cognitive theory and knowledge, attitude/belief, practice theory, the first draft of the evaluation index system for health management effects of high-risk stroke groups was drawn up by literature review and group discussion. Through two rounds of Delphi expert consultation, the evaluation index system of health management effects of high-risk stroke groups was established, and the weight of each index was determined by analytic hierarchy process (AHP). A total of 22 experts were invited to participate in expert consultation. Twenty-two questionnaires were sent out in the first round, and 20 questionnaires were recovered, of which 20 were valid (90.9%). In the second round of correspondence, 20 questionnaires were sent out and 19 questionnaires were recovered, of which 19 were valid (95.0%).Results:The authority coefficients of the two rounds of expert consultation (Cr) was 0.933 and 0.937, respectively. The Kendall coordination coefficients W of importance in the second round was significantly higher than that in the first round (0.299 vs 0.172) ( P<0.001). The mean of importance score (Mj) of each index was 4.10-5.00, coefficient of variation (CV) was 0-0.235, and full mark ratio (Kj) was 0.26-1.00. Finally, an evaluation index system of the health management effects for high-risk stroke population was constructed, which included 3 first-level indicators (individual characteristics, behavior style, environmental support), 12 second-level indicators and 58 third-level indicators. Conclusions:The evaluation index system of the health management effects for high-risk stroke population is established in this study, which provides scientific quantitative indicators and evaluation tools. The enthusiasm, authority and coordination of consultation experts are strong, which indicates that the indicator system is feasible.
7.PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway.
Peihua LIU ; Ling JIANG ; Weimin KONG ; Qiushi XIE ; Ping LI ; Xiaonan LIU ; Jiayi ZHANG ; Ming LIU ; Zhongjian WANG ; Liang ZHU ; Hanyu YANG ; Ying ZHOU ; Jianjun ZOU ; Xiaodong LIU ; Li LIU
Acta Pharmaceutica Sinica B 2022;12(5):2391-2405
Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.
8.Investigation and analysis of thyroid nodules and goiter in school-age children in different water iodine areas of Jiangsu Province
Yuting XIA ; Li SHANG ; Yunjie YE ; Yang WANG ; Mao LIU ; Peihua WANG ; Yan XU
Chinese Journal of Endemiology 2022;41(10):819-823
Objective:To analyze the detection rate of thyroid nodules and goiter in school-age children in different water iodine regions and investigate the difference of thyroid nodule and goiter in school-age children with different age, gender and body mass index (BMI) in Jiangsu Province.Methods:In 2017, three villages with water iodine values of 8.1, 51.2 and 115.4 μg/L (iodine deficient group, iodine appropriate group and iodine high group) were selected as survey sites in Xuzhou City, Jiangsu Province, where the supply of iodized salt was suspended. One primary school was selected from each village, and children aged 8 to 10 years old (age balance, half male and half female) were selected from each primary school as the survey subjects. Urine sample were collected, urinary iodine level was determined, height and weight were measured, and neck B ultrasound was performed.Results:A total of 131, 140 and 138 school-age children aged 8 to 10 years old were investigated in the iodine deficient group, iodine appropriate group and iodine high group, respectively, with a total of 409 children. The detection rates of thyroid nodules were 6.9% (9/131), 15.0% (21/140) and 16.7% (23/138), respectively, and the detection rates of goiter were 1.5% (2/131), 1.4% (2/140) and 6.5% (9/138) in the three groups, respectively. There were statistically significant differences in the detection rates of thyroid nodules and goiter in different water iodine groups (χ 2 = 6.92, 6.37, P < 0.05). The detection rates of thyroid nodules in different age groups were 9.5% (12/126), 11.3% (16/142) and 17.7% (25/141), the differences were statistically significant (χ 2 = 9.05, P < 0.05). The detection rates of thyroid nodules were 11.6% (24/207), 14.4% (29/202), and 12.5% (39/313), 16.9% (14/83), 0/9 and 0/4 in the subjects of different gender and BMI, the differences were not statistically significant (χ 2 = 0.69, P > 0.05). The detection rates of goiter in the subjects of different gender, age and BMI were 1.4% (3/207), 5.0% (10/202); 2.4% (3/126), 6.3% (9/142), 0.7% (1/141); 1.6% (3/313), 4.8% (4/83), 3/9 and 1/4. The differences were statistically significant (χ 2 = 4.07, 7.66, P < 0.05). Conclusion:The detection rate of thyroid nodules in school-age children in different water iodine regions in Jiangsu Province may have a certain relationship with age, and the detection rate of goiter may have a certain relationship with age, gender and BMI.
9.Effectiveness evaluation of health education on drinking-water-borne endemic fluorosis in Jiangsu Province from 2014 to 2018
Yuting XIA ; Yunjie YE ; Mao LIU ; Li SHANG ; Peihua WANG ; Yang WANG
Chinese Journal of Endemiology 2022;41(11):929-933
Objective:To evaluate the effect of health education on drinking-warter-borne endemic fluorosis in Jiangsu Province.Methods:From 2014 to 2018, a total of 12 counties (districts) with drinking-warter-borne endemic fluorosis were selected to carry out public health education activities, and 3 townships were chosen in each project county (district). School health education activities were carried out in the classes of grade 4 - 6 in the central primary school in each selected twonship. In the meantime, 3 villages were chosen in each selected township where the health education activities in the community were carried out. Before and after the health education activities, questionnaire surveys on knowledge of drinking-warter-borne endemic fluorosis prevention were conducted among 30 students in one class of grade 5 in the central primary school and 15 housewives lived near the central primary school in each township.Results:After the health education activities, the rates of knowledge awareness in the students and the housewives were 94.83% (15 362/16 200) and 95.14% (7 706/8 100), respectively, which were significantly higher than those before the health education activities [63.88% (10 348/16 200) and 65.94% (5 341/8 100)], and the differences were statistically significant (χ 2 = 4 700.00, 2 200.00, P < 0.001). There were no statistical differences in the rates of knowledge awareness in the students and housewives before the health education activities from 2014 to 2018 (χ 2 = 8.43, 0.88, P = 0.077, 0.928). Before the health education activities, the rate of knowledge awareness in the students was lower than that in the housewives, and the difference was statistically significant (χ 2 = 10.03, P = 0.002). After the health education activities, there was no statistical difference between the rate of knowledge awareness in the students and that in the housewives (χ 2 = 1.07, P = 0.301). Conclusions:The rates of knowledge awareness in the students and the housewives are increased significantly after the health education activities. We should expand the coverage of health education. Wide, deep and persistent health education in more ways for different people are needed to consolidate the achievements.
10.PSC-MSC-Derived Exosomes Protect against Kidney Fibrosis In Vivo and In Vitro through the SIRT6/β-Catenin Signaling Pathway
Limin LIU ; Yao WU ; Pingan WANG ; Min SHI ; Juning WANG ; Huaifen MA ; Dangze SUN
International Journal of Stem Cells 2021;14(3):310-319
Background and Objectives:
Chronic kidney disease (CKD) has a major impact on the quality of life of patients, and renal fibrosis is a critical pathological change in the disease. It is very important to control the process of renal fibrosis to improve the quality of life of patients with CKD. The pathological mechanism of renal fibrosis is very complicated, and the current treatment strategy also has many flaws.
Methods:
and Results: To explore a better treatment, we collected exosomes from pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSC) and verified their therapeutic effect on renal fibrosis through In Vivo and In Vitro experiments. In this study, we found that PSC-MSC-derived comes could prevent the epithelial differentiation of NRK-52E cells, and with increasing exosome concentrations, the effect was improved. Furthermore, PSC-MSC-derived exosomes could reduce the pathological process of renal fibrosis, reduce inflammatory reactions and improve renal function in UUO mice. Moreover, the protective effect of exosomes against renal fibrosis may be achieved by increasing the expression of SIRT6 and decreasing the expression of β-catenin and its downstream products.
Conclusions
These findings suggest the possibility of PSC-MSC-derived exosomes as a new, effective therapeutic tool for kidney fibrosis.

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