1.Mechanism of Paeonol in Alleviating Alcohol-induced Liver Injury in Mice Through Regulating SCFAs-GPR43/MAPK Signaling Pathway Mediated by Intestinal Flora
Shengnan JIANG ; Qifeng WU ; Zining WANG ; Hao PU ; Guiming YAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):129-139
ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids (SCFAs)-specific receptor GPR43/mitogen-activated protein kinase (MAPK) signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups: blank control group, model group, low-dose paeonol group (120 mg·kg-1), high-dose paeonol group (480 mg·kg-1), and silybin group (36.8 mg·kg-1). A mouse model of alcohol-induced liver disease (ALD) was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels, liver function, inflammatory cytokines, and oxidative stress markers were measured. Liver hematoxylin-eosin (HE) staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 (ZO-1), Claudin-1, and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43, ZO-1, and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group, the model group showed significantly elevated serum lipid levels, oxidative stress, and inflammatory cytokine expression (P<0.01). Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated (P<0.01), while GPR43, ZO-1, and Claudin-1 protein expression levels were significantly decreased (P<0.01). The composition and abundance of the intestinal flora were markedly altered, with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium, Parabacteroides, Erysipelothrix, and Adlercreutzia, alongside increased abundances of Clostridium butyricum, Enterococcus, and Helicobacter pylori in the model group. Compared with the model group, paeonol significantly reduced serum lipid levels, oxidative stress responses, and the expression of inflammatory cytokines in ALD mice (P<0.05, P<0.01). It also attenuated hepatic lipid accumulation, restored intestinal barrier function, and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1, Claudin-1, and GPR43 in the colonic tissue were significantly increased (P<0.05, P<0.01), while those of MAPK pathway-related proteins were significantly decreased (P<0.05, P<0.01). The intestinal flora dysbiosis was effectively alleviated, rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments, supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice, which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway, thereby achieving anti-inflammatory effects and improving intestinal barrier function.
2.Mechanism of Paeonol in Alleviating Alcohol-induced Liver Injury in Mice Through Regulating SCFAs-GPR43/MAPK Signaling Pathway Mediated by Intestinal Flora
Shengnan JIANG ; Qifeng WU ; Zining WANG ; Hao PU ; Guiming YAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):129-139
ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids (SCFAs)-specific receptor GPR43/mitogen-activated protein kinase (MAPK) signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups: blank control group, model group, low-dose paeonol group (120 mg·kg-1), high-dose paeonol group (480 mg·kg-1), and silybin group (36.8 mg·kg-1). A mouse model of alcohol-induced liver disease (ALD) was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels, liver function, inflammatory cytokines, and oxidative stress markers were measured. Liver hematoxylin-eosin (HE) staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 (ZO-1), Claudin-1, and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43, ZO-1, and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group, the model group showed significantly elevated serum lipid levels, oxidative stress, and inflammatory cytokine expression (P<0.01). Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated (P<0.01), while GPR43, ZO-1, and Claudin-1 protein expression levels were significantly decreased (P<0.01). The composition and abundance of the intestinal flora were markedly altered, with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium, Parabacteroides, Erysipelothrix, and Adlercreutzia, alongside increased abundances of Clostridium butyricum, Enterococcus, and Helicobacter pylori in the model group. Compared with the model group, paeonol significantly reduced serum lipid levels, oxidative stress responses, and the expression of inflammatory cytokines in ALD mice (P<0.05, P<0.01). It also attenuated hepatic lipid accumulation, restored intestinal barrier function, and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1, Claudin-1, and GPR43 in the colonic tissue were significantly increased (P<0.05, P<0.01), while those of MAPK pathway-related proteins were significantly decreased (P<0.05, P<0.01). The intestinal flora dysbiosis was effectively alleviated, rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments, supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice, which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway, thereby achieving anti-inflammatory effects and improving intestinal barrier function.
3.Inhibition of Alcoholic Liver Injury by Paeonol Through Eubacterium-mediated TGR5/PKA/CREB Signaling Pathway
Luning ZHANG ; Lingling LIU ; Shengnan JIANG ; Qifeng WU ; Guiming YAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):78-86
ObjectiveTo investigate whether paeonol exerts a protective effect on mice with alcoholic liver injury by regulating the takeda G-protein-coupled receptor 5 (TGR5)/protein kinase A (PKA)/cAMP response binding element (CREB) signaling pathway mediated by Eubacterium. MethodC57BL/6 mice were randomly divided into five groups: normal group, model group, paeonol group (480 mg·kg-1), antibiotic group (Abs group), and antibiotic + paeonol group. Lieber-DeCarli liquid was used to feed C57BL/6 mice on the second day of modeling for 10 days. The blood lipids, liver function, inflammatory factors, and oxidative stress levels in mice were measured. Hematoxylin-eosin staining (HE) and oil red O staining were used to observe the morphological changes and fat accumulation in liver tissue. 16S rDNA sequencing was used to detect the diversity of intestinal microbiota in the blank, model, and paeanol groups. Western blot was used to detect the effect of paeonol on the expression levels of protein related to the signaling pathway of atresia band protein 1 (ZO-1), Claudin-1, and TGR5/PKA/CREB in mouse ileal tissue. ResultCompared with those in the blank group, the blood lipids, liver function, oxidative stress levels, and the expression of inflammatory factors in the model group increased (P<0.01), and the liver fat vacuoles were obvious. The ileal mucosa was seriously damaged, and the protein contents of ZO-1, Claudin-1, and TGR5/PKA/CREB in the ileal tissue decreased significantly (P<0.01). The intestinal microbiota changed, and the proteobacteria phylum increased significantly. The ratio of Bacteroidetes to Firmicutes decreased. The relative abundance of Dubosiella newyorkensis, Lactobacillus, Bifidobacterium, and other genera decreased, while the relative abundance of Escherichia-Shigella, Morganella, Providencia, and Proteus increased significantly. Compared with the model group, paeonol significantly reduced the blood lipids, liver function, oxidative stress levels, and expression of inflammatory factors in mice with alcohol diet-induced liver injury (P<0.05), decreased liver fat vacuoles, improved and restored the ileal intestinal barrier, and restored the normal structure of hepatocytes and ileal cells. The intestinal microbiota disorder caused by alcohol was improved, and the relative abundance of beneficial bacteria such as Eubacterium spp. was increased. The protein expression levels of ZO-1, Claudin-1, and TGR5/PKA/CREB in ileal tissue were increased (P<0.05). ConclusionPaeonol has a protective effect on alcoholic liver injury in mice, and the mechanism of action is achieved by regulating the Eubacterium-mediated TGR5/PKA/CREB signaling pathway to ensure anti-inflammatory effect and improve the intestinal barrier.
4.Using Instrumental Approach to Estimate the Effect of PM2.5 Concentrations on Daily Deaths
Guiming ZHU ; Haosen YAN ; Tong WANG
Chinese Journal of Health Statistics 2024;41(4):526-531,538
Objective Many environmental epidemiological studies have shown the associations between short-term exposure of air pollution and daily deaths.However,the generally available population data only contain a small number of measured confounding factors,which is faced with the problem that a large number of unobserved confounding factors are not included in the model,resulting in biased estimates.The instrumental variable method can solve the problem of estimating the effects caused by unobserved confounders.In this paper,We used the instrumental variable method to estimate the effects of PM2.5 on daily mortality.Methods We collected daily PM2.5 concentrations,meteorological data,and nonaccidental daily deaths in a Chinese city from 2016 to 2019.We used boundary layer height and wind speed as instrumental variables to estimate the effects of PM2.5 on nonaccidental daily mortality.Negative exposure control was used to test the hypothesis of instrumental variables.Meanwhile time series bootstrap method was used to estimate confidence interval.We compared the results of the generalized additive model and instrumental variable method.Results The instrumental variable method showed that PM2.5 was significantly related to daily deaths.For every 10 μg/m3 increase of PM2.5 concentrations,the nonaccidental daily deaths increased by 0.94%(95%CI:0.39%~1.55%).Negative exposure control results showed no correlation between negative exposure and nonaccidental deaths(P=0.19),indicated that the aforementioned instrumental variable model was not affected by unmeasured and uncontrolled confounders.The traditional generalized additive model estimated that for every 10 μg/m3 increase in PM2.5 concentrations,the nonaccidental deaths would increase by 0.24%(95%CI:0.01%~0.47%).Conclusion The instrumental variable method estimated that PM2.5 concentrations were significantly correlated with the nonaccidental daily deaths.Boundary layer height and wind speed can be used as instrumental variables to estimate the effects of PM2.5 concentrations on nonaccidental deaths.
5. Exploration and implementation on the mode of undergraduate community nursing practice, according to "National Standard of Undergraduate Teaching Quality"
Jingrui XU ; Guiming YAN ; Shan ZHAO ; Chunmei WANG ; Yue ZHAO ; Qi LU
Chinese Journal of Practical Nursing 2019;35(22):1681-1684
According to 'National Standard of Undergraduate Teaching Quality for Nursing Science', the mode of community nursing practice was explored and implemented by the School of Nursing in Tianjin Medical University. Focus on competency, the syllabus of community nursing practice was revised. Optimizing the management system of community nursing practice, developing the team of high-quality teachers, building standardized community nursing practice bases, and improving the evaluation system of community nursing practice aimed to enhance comprehensive quality of nursing undergraduates and the quality of community nursing practice. Within the concept of "big health", our school is exploring the new mode of combining community nursing practice with health management-oriented nursing personnel training, which lays an important foundation for training applied nursing talents to meet the needs on development of community health services.
6.Clinical application of new type individualized fixation device for radiotherapy of rectal cancer
Guofu CHEN ; Guiming YAN ; Feiyan ZHANG
Chinese Journal of Primary Medicine and Pharmacy 2019;26(1):2-5
Objective To explore the clinical effect of new type rectal cancer radiotherapy individualized fixation device in the radiotherapy of rectal cancer. Methods From June 2015 to December 2016,60 patients with rectal cancer who accepted the external irradiation in Zhejiang Tumor Hospital were divided into two groups by random number table method. A group(31 cases) received new type rectal cancer radiotherapy position fixation devices with thermoplastic film. B group(29 cases) received simple foam pad with thermoplastic film. Before each treatment,Cone beam CT(CBCT) scan was conducted. The applied CBCT image and the planned reconstruction image were compared in the direction of X(left and right),Y(upper and lower)and Z(front and rear) axis. The setup error was recorded, and the correlation between the two groups was analyzed. Results The average setup error of patients in A group in X (left and right),Y(upper and lower),Z(front and rear) axis were (1. 61 ± 0. 18)mm,(1. 82 ± 0. 13)mm,(1. 91 ± 0. 11)mm,respectively. The average setup error of patients in B group in X(left and right),Y(upper and lower),Z (front and rear) axis were (2. 22 ± 0. 13)mm,(2. 43 ± 0. 14)mm,(2. 36 ± 0. 13)mm,respectively. There were statistically significant differences between the two groups(t=14. 958,17. 501,11. 283,all P<0. 001). Conclusion The new type of rectal cancer radiotherapy position fixing device is more comfortable than the simple foam pad,and the setting error is smaller than the simple foam pad.
7.Laparoscopic pancreaticoduodenectomy via a "G "-shaped approach: experience of 33 cases
Zhigang WEI ; Yuxuan WEI ; Tianyu HUO ; Yu LIU ; Jie YU ; Hao YAN ; Guiming WANG
Chinese Journal of General Surgery 2018;33(7):575-577
Objective To investigate the feasibility and safety of "G"-shaped surgical approach in laparoscopic pancreaticoduodenectomy.Methods The clinical data of 33 patients who received " G"-shaped laparoscopic pancreaticoduodenectomy in the First Hospital of Shanxi Medical University from April 2015 to March 2018 were retrospectively analyzed.Results All patients underwent surgery successfully.The time required for surgery ranged from 340 to 498 min,the blood loss ranged from 150 to 800 ml,and the specimen resection time ranged from 135 to 270 min.There were 10 cases of biochemical leakage,3 cases of B grade pancreatic fistula and 1 case of bile leak.Postoperative pathology confirmed lower bile duct adenocarcinoma in 17 cases,duodenal papillary adenocarcinoma in 11 cases and poorly differentiated adenocarcinoma of the pancreatic head in 5 cases.Conclusions " G"-shaped approach as a simple,effective and safe way for LPD,is particularly helpful for inexperienced hands.
8.Occupational exposure among health care workers in a hospital
Guiming WANG ; Ling YAN ; Ling ZHANG ; Shengmei LAN
Chinese Journal of Infection Control 2015;(4):265-267
Objective To understand the characteristics of population distribution,risk factors and risk links of occupational exposure among health care workers(HCWs)in a hospital.Methods Occupational exposure among HCWs between January 2011 and June 2014 were monitored,data about occupational categories of HCWs,expo-sure locations,exposure links and exposure modes were analyzed statistically.Results Among 286 occupational ex-posure cases,the female and male HCWs accounted for 22.03% (n=63)and 77.97% (n=223)respectively;the incidence of occupational exposure in 2011 ,2012,2013 and January-June of 2014 was 38.81 %(n=111),26.22% (n=75),23.43% (n=67)and 11 .54% (n=33)respectively;occupational exposure of junior nurses,doctors,nurs-ing attendants,technicians,senior nurses and cleaners was 31 .97%,19.90%,15.79%,7.64%,4.17%,and 2.84% respectively;exposure mainly occurred at the time of sorting waste,withdrawing or changing needles,dis-carding sharps into sharps containers,surgical suturing or instruments passing,and puncturing (including drawing blood),the constituent ratio was 22.38%,19.58%,14.34%,12.94% and 11 .19%,respectively;the main loca-tions where exposure occurred were wards,operating rooms and injection (treatment)rooms,the constituent ratio was 51 .40%,19.58% and 11 .54% respectively.Conclusion Hospital should establish comprehensive occupational exposure monitoring and risk management system,strengthen standard prevention,enhance the training about occu-pational exposure among high-risk population,and monitor and intervene on risk factors and links,so as to reduce the incidence of HCWs’occupational exposure.
9.Analysis on set-up errors of position fixation with simple perforated foam pad in colorectal cancer radio-therapy
Guofu CHEN ; Binbing WANG ; Linming FANG ; Feiyan ZHANG ; Guiming YAN ; Chai ZHOU ; Long SUN ; Qiangke ZHANG ; Guoping SHAN ; Jialin LUO
Chinese Journal of Primary Medicine and Pharmacy 2015;(17):2561-2563
Objective To explore the set-up errors of position fixation with simple perforated foam pad in colorectal cancer radiotherapy and their causes as well as the improvement measures.Methods Sixty cases of color-ectal cancer patients undergoing radiotherapy were collected.Prone position was adopted with the position fixed by perforated foam pad and membrane.CBCT imaging was taken weekly before treatment,setup errors were corrected if necessary.Errors throughout the course of treatment for each patient were recorded and compared between patients, followed by analyzing the reasons of errors.Results Before calibration,the maximum errors on the direction of left and right (X-axis),front and back (Z),upside and downside (Y)in these 60 patients were 0.5cm,0.9cm and 0.7cm respectively with the average errors of (0.22 ±0.03)cm,(0.38 ±0.03)cm and (0.27 ±0.04)cm respec-tively.Conclusion The method of applying perforated foam pad and thermoplastic mask in colorectal cancer radio-therapy is currently the most commonly used in the clinical position fixation techniques,by which the small intestine, bladder and other pelvic tissues can be well protected.Due to poor comfort prone position,it is necessary to further improve perforated foam pad through improving the quality of the foam pad,thus improving patients comfort and posi-tioning repeatability and reducing position fixation errors.
10.Analysis of the influence factors of central venlus catheters-related infections in postoperative patients with gastric carcinoma treated with parenteral nutrition
Yanxia TAO ; Yue ZHAO ; Na SHU ; Guiming YAN
Chinese Journal of Practical Nursing 2015;31(22):1662-1665
Objective To investigate the influence factors of central venous catheter related infections (CVC-RI) in postoperative patients with gastric carcinoma treated with parenteral nutrition,in order to provide scientific basis for prevention and treatment.Methods Using the retrospective study method,150 patients who treated with parenteral nutrition after operation of gastric carcinoma from December 2013 to March 2014 were selected.Information including age,sex,anamnesis,catheter indwelling time,infusion rate of nutrient solution,and so on were collected.Patients with central venous catheter related infections were set as infection group,patients without infection as the control group,and the group logistic regression analysis was used to analyze the collected data.Results 21 patients in infection group had CVC-RI,and the incidence was 14.00% (21/150),while 129 patients in control group had CVC-RI.Univariate analysis showed there was significant difference between infection group and control group in age,anamnesis,catheter indwelling time and infusion rate of nutrient solution (x2=17.126,5.447,12.795,7.973,P<0.05),however there was no significant difference in sex,health insurance,the success rate of catheterization and whether glutamine was in nutrient solution (P>0.05);the group logistic regression analysis showed that age (OR=15.927,95%CI 3.305-76.756,P<0.05)and catheter indwelling time (OR=3.511,95%CI 1.028-11.992,P<0.05) were independent risk factors for CVC-RI,however infusion rate of nutrient solution (OR=0.140,95%CI 0.033-0.597,P<0.05) was a protective factor.Conclusions For the postoperative patients with gastric carcinoma treated with parenteral nutrition,CVC-RI is closely related to age,catheter indwelling time and infusion rate of nutrient solution.So reducing catheter indwelling time,restoring the enteral nutrition under condition permission as so on as possible can reduce infection of elderly patients.

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