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.Clinical analysis on the diagnosis and treatment of a patient with metallic mercury poisoning from subcutaneous injection by ultrasonography
Xiaozhen XIANG ; Ziwen CAO ; Zongguang LIU ; Aichu YANG ; Qifeng WU
China Occupational Medicine 2025;52(3):304-307
To analyze the clinical data and imaging examination data of a patient with metallic mercury poisoning from subcutaneous injection. The abdominal B-ultrasonograph results of the patient indicated multiple scattered hyperechoic spots accompanied by "comet tail" sign in the liver and right renal sinus, the nature of which was not clear and it was considered crystal deposition. The chest X-ray revealed scattered and multiple spot-like, snowflake-like and tree-cast-like high-density shadows in both lung fields. The chest computed tomography scan revealed multiple spot and patchy high-density shadows distributed in both lungs, considering hematogenous distribution deposits, and possible mercury poisoning. Laboratory test results showed that blood mercury level was 4.16 μmol/L and urine mercury level was 6 545.5 μg/g Cr. After 28 days of mercury chelation therapy, the abdominal ultrasound examination showed that the hyperechoic spots in the liver and right renal sinus were reduced compared with the previous examination. Metallic mercury poisoning from subcutaneous injection has specific manifestations in abdominal B-ultrasound imaging, which can provide a basis for the early diagnosis of metallic mercury poisoning in clinical practice and can be used to observe the efficacy of mercury chelation therapy.
4.Metagenomics reveals an increased proportion of an Escherichia coli-dominated enterotype in elderly Chinese people.
Jinyou LI ; Yue WU ; Yichen YANG ; Lufang CHEN ; Caihong HE ; Shixian ZHOU ; Shunmei HUANG ; Xia ZHANG ; Yuming WANG ; Qifeng GUI ; Haifeng LU ; Qin ZHANG ; Yunmei YANG
Journal of Zhejiang University. Science. B 2025;26(5):477-492
Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged
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Aged, 80 and over
;
Female
;
Humans
;
Male
;
Middle Aged
;
Bacteroides
;
China
;
Diabetes Mellitus, Type 2/microbiology*
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Escherichia coli/classification*
;
Gastrointestinal Microbiome/genetics*
;
Metagenomics
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East Asian People
5.Advancements and applications in radiopharmaceutical therapy.
Shiya WANG ; Mingyi CAO ; Yifei CHEN ; Jingjing LIN ; Jiahao LI ; Xinyu WU ; Zhiyue DAI ; Yuhan PAN ; Xiao LIU ; Xian LIU ; Liang-Ting LIN ; Jianbing WU ; Ji LIU ; Qifeng ZHONG ; Zhenwei YUAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):641-657
Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including 223Ra, 90Y, Lutetium-177 (177Lu), 212Pb, and Actinium-225 (225Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans
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Radiopharmaceuticals/therapeutic use*
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Neoplasms/radiotherapy*
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Radioisotopes/therapeutic use*
;
Animals
6.Investigation of a group occupational acute dimethylacetamide poisoning incident
Jian HUANG ; Xiaoyong LIU ; Jintong HE ; Jiaheng HE ; Qifeng WU ; Jiaxin JIANG
China Occupational Medicine 2024;51(4):476-480
Objective To investigate and analyze a group occupational acute dimethylacetamide (DMA) poisoning incident occurred during the post-fire cleaning operation in a spandex manufacturing enterprise. Methods This study focused on the involved enterprise, employing units, poisoning patients, and workers with similar occupational exposure history from a group occupational acute chemical poisoning incident in Guangdong Province in 2023. Occupational health on-site investigation data, clinical records of poisoned patients, and occupational disease diagnostic data were collected to determine the cause of the poisoning. Results The incident occurred at a spandex manufacturing enterprise during the cleaning of polymerization reaction vessels after a fire, resulting in poisoning of six cleaning workers. The clinical symptoms of patients included varying degrees of liver function abnormalities and skin damage. All six patients wore long-tube air-supplied full-face masks during work. The patients were in a confined work space with poor ventilation, and worked more than 8 hours per day. Patients felt unwell after 5-13 days of work. Post-incident investigation revealed that the DMA exposure concentration of short term near the reaction vessels was 36.06 mg/m³. DMA accounted 13.74% to 30.09% of the volatile organic compounds in the raw and auxiliary materials and waste in the vessel. N-methylacetamide was detected in the urine of these six patients, with levels up to 1 639.78 mg/g creatinine, exceeding the occupational exposure limit (20.00 mg/g creatinine). All six patients were diagnosed as occupational acute DMA poisoning. Conclusion Occupational acute DMA poisoning mainly causes liver damage, has a latent onset, and poses a risk of group occurrence. The main causes of group poisoning are confined work space, inadequate management, insufficient protective measures, and excessive working hours.
7.Impact of optimizing stroke green channel on treatment efficiency of acute ischemic stroke treatment efficiency in a county hospital
Yao WANG ; Lei SHI ; Guangbu LI ; Qiyun ZHU ; Xiaoqiang WU ; Maolin LU ; Haiyang LIN ; Wei QI ; Wei GAO ; Ruiyin ZHOU ; Qifeng LU ; Baodong WU
Chinese Journal of Clinical Medicine 2024;31(6):971-976
Objective To evaluate the impact of optimizing the stroke green channel on the efficiency of acute ischemic stroke management in a county hospital. Methods A retrospective analysis of the emergency stroke green channel treatment data from Sixian People’s Hospital from May 2020 to April 2021 (before optimization of the green channel) and from May 2021 to April 2022 (after optimization of the green channel) was conducted. The rates of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) patients, as well as door-to-needle time (DNT), door-to-puncture time (DPT), and the modified Rankin scale (mRS) scores of patients three months post-treatment before and after the optimization of the stroke green channel were compared. Results Within one year before and after optimization of the green channel, the number of acute visits for ischemic stroke was 3 143 and 2 623, respectively. Before optimization, 84 and 51 underwent IVT and MT, respectively. After optimization of the green channel, the ratios of patients underwent IVT (n=215) and MT (n=103) significantly increased, and both DNT and DPT were significantly shortened (P<0.000 1); the proportion of MT patients with an mRS score of 0-2 at 3 months post-discharge significantly increased (46/99 vs 13/46, P=0.038). Conclusion After optimizing the green channel at Sixian People’s Hospital, the efficiency of stroke treatment has significantly improved, and the patients’ prognosis improved.
8.Endoscopic submucosal dissection for the treatment of gastric fundus adenocarcinoma(4 cases)
Yangqing WU ; Jianbo ZHOU ; Ying FANG ; Jianzhong SANG ; Qifeng SONG ; Jian HUANG
China Journal of Endoscopy 2024;30(8):80-84
Objective To summarize the endoscopic and clinical diagnosis and treatment of 4 cases of gastric fundus adenocarcinoma.Method A retrospective analysis was conducted on the clinical data of four cases of gastric fundus adenocarcinoma from July 2021 to December 2023.Result All the 4 cases of gastric fundus adenocarcinoma were completely removed by endoscopic submucosal dissection(ESD),with good postoperative recovery,no surgical complications,and no recurrence or metastasis during follow-up.Conclusion ESD treatment for gastric fundus adenocarcinoma is safe,reliable,and can completely remove the lesion.
9.Introduction to the revision of Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene
Lihua XIA ; Ying ZHANG ; Xiaofeng DENG ; Shanyu ZHOU ; Yongshun HUANG ; Xiying LI ; Qifeng WU ; Muwei CAI ; Xiaowen LUO ; Fengling ZHAO
China Occupational Medicine 2024;51(1):37-42
With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.
10.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.

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