1.Effect of Huanglian Jiedutang in Regulating Ferroptosis in Mice with Atherosclerosis Based on Nrf2/GPX4 Signaling Pathway
Zhaohui GONG ; Li GAO ; Huiqi ZHAI ; Jinzi YU ; Qingmin CHU ; Chuanjin LUO ; Lijin QING ; Wei WU ; Rong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):22-28
ObjectiveTo study the mechanism of Huanglian Jiedutang (HLJDT) in treating mice with atherosclerosis (AS) by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group, and 50 ApoE-/- mice were randomly divided into five groups: model group, low-dose group of HLJDT, medium-dose group of HLJDT, high-dose group of HLJDT, and atorvastatin (ATV) group. ApoE-/- mice were fed a high-fat diet for eight weeks to establish the AS model, and at the 9th week, they were given normal saline, low, medium, and high doses of HLJDT (3.9, 7.8, 15.6 g·kg-1·d-1), and atorvastatin calcium tablets (0.01 g·kg-1·d-1), respectively, for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in blood fat were measured by the automatic biochemical analyzer, and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase (SOD) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The content of reduced glutathione (GSH) in serum was detected by the microplate method, and that of malondialdehyde (MDA) in serum was detected by the TBA method. The protein expression of nuclear factor E2-associated factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway was detected by Western blot. ResultsCompared with those of the normal group, the contents of TC, LDL-C, TG, HDL-C, and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased (P<0.01), while the expression levels of SOD and GSH in serum, as well as Nrf2, solute carrier family 7 member 11 (SLC7A11), and GPX4 in aorta were significantly decreased (P<0.01). Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta, volume atrophy, mitochondrial crista reduction, or a loose and disorganized form. Compared with those in the model group, the aortic vascular plaque deposition was significantly decreased in the low-dose, medium-dose, and high-dose groups of HLJDT and ATV group, and the contents of serum TC, LDL-C, TG, and MDA in serum were significantly decreased (P<0.05, P<0.01). The contents of serum SOD and GSH and the expression levels of Nrf2, SLC7A11, and GPX4 in the aorta were increased (P<0.05, P<0.01), and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased, and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition, decrease blood lipid and MDA expression, increase SOD and GSH expression, and ameliorate the pathological changes of ferroptosis, the mechanism of which is related to the Nrf2/GPX4 signaling pathway.
2.The Effect of Banxia Xiexin Decoction (半夏泻心汤) on the Expression of LXRα in Liver Tissue and the JAK2/STAT3 Signaling Pathway in Gastric Antrum Tissue of Diabetic Gastroparesis Model Rats
Qi XU ; Nuobing RUAN ; Jinju LI ; Xijuan LYU ; Zhaohui FANG
Journal of Traditional Chinese Medicine 2025;66(2):178-187
ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction (半夏泻心汤, BXD) in the treatment of diabetic gastroparesis (DGP). MethodsA total of 29 SD rats were randomly divided into four groups, blank group (5 rats) and model group, BXD group and metformin group (8 rats in each group). Except for the blank group, rats were administered intraperitoneally with 1% streptozotocin (STZ) solution and were fed a high-sugar, high-fat diet to establish the DGP rat model. After successful modeling, the BXD group was treated with BXD at 6.68 g/(kg·d) by gavage, the metformin group was treated with metformin hydrochloride at 105 mg/(kg·d) by gavage, and the blank group and the model group were treated with normal saline at 6.68 ml/(kg·d) by gavage, for 8 weeks. After the last administration, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG) were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin (MTL) and gastrin (GAS), as well as inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin (HE) staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α (LXRα) levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue, and of janus kinase 2 (JAK2), phospho-janus kinase 2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3) and phospho-signal transducer and activator of transcription 3 (p-STAT3) in gastric antrum tissue. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of LXRα in liver tissue and JAK2, STAT3 in gastric antrum tissue. ResultsCompared with the blank group, the model group showed significant hepatic fatty degeneration, gastric antrum tissue structure destruction, and increases in FBG, HbA1c, TC, and TG levels; the average fluorescence intensity, protein level, and mRNA expression of LXRα in liver tissue were reduced; the gastric emptying rate and gastric tissue GAS and MTL levels decreased; inflammatory factors including TNF-α, IL-6, IL-1β in gastric tissue increased, IL-10 decreased; in gastric antrum tissue, the mRNA expression of p-JAK2/JAK2, p-STAT3/STAT3, and JAK2 and STAT3 increased (P<0.01). Compared with the model group, both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology; FBG, HbA1c, TC, and TG levels decreased, while LXRα fluorescence intensity, protein level, and mRNA expression in liver tissue significantly increased; the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher; the levels of TNF-α, IL-6, and IL-1β decreased, whereas IL-10 levels increased, p-JAK2/JAK2, p-STAT3/STAT3, and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased (P<0.05 or P<0.01). The BXD group showed higher level than the metformin group in FBG, HbA1c, and TG levels, lower level in gastric emptying rate and gastric tissue GAS content, and higher level in gastric tissue TNF-α, IL-6, IL-1β levels; there was also a decrease in IL-10 levels, and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue, as well as in p-JAK2/JAK2 levels in gastric antrum tissue (P<0.05 or P<0.01). ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.
3.Internal tension relieving technique assisted anterior cruciate ligament reconstruction to promote ligamentization of Achilles tendon grafts in small ear pigs in southern Yunnan province
Bohan XIONG ; Guoliang WANG ; Yang YU ; Wenqiang XUE ; Hong YU ; Jinrui LIU ; Zhaohui RUAN ; Yajuan LI ; Haolong LIU ; Kaiyan DONG ; Dan LONG ; Zhao CHEN
Chinese Journal of Tissue Engineering Research 2025;29(4):713-720
BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).
4.An excerpt of ESMO clinical practice guideline interim update on the management of biliary tract cancer in 2025
Delong QIN ; Yue TANG ; Zonglong LI ; Jialu CHEN ; Zhaohui TANG ; Zhiwei QUAN
Journal of Clinical Hepatology 2025;41(4):625-627
In January 2025, the European Society for Medical Oncology (ESMO) released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines, and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.
5.A systematic evaluation of the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces
Huayi ZHANG ; Qingyu ZHOU ; Huihui HUANGFU ; Peiwu SHI ; Qunhong SHEN ; Chaoyang ZHANG ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Anning MA ; Zhaohui GONG ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Chao HAO ; Zhi HU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):451-457
ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.
6.Observation of corneal cell in diabetic patients using in vivo confocal microscopy
Lingrui MENG ; Wenqian CHEN ; Yi GAO ; Zi YE ; Zhaohui LI
International Eye Science 2024;24(5):664-670
In vivo confocal microscopy of the cornea is a non-invasive, rapid, and comprehensive technique for real-time, dynamic observation of all layers of the cornea. Confocal microscopy allows the examination of the morphology and cell density in the different layers of the cornea through direct visualization. With the increasing prevalence of diabetes, ocular complications have become common and have garnered more interest and in-depth research from clinical and scientific communities. This paper provides a comprehensive review of research progress made using in vivo confocal microscopy to observe various layers of cornea tissue in diabetic patients.
7.Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia
Zhaohui WANG ; Xiao LIU ; Yue ZHOU ; Xinyi WEI ; Yue WANG ; Junfa LI ; Li ZHAO
Basic & Clinical Medicine 2024;44(2):167-173
Objective To explore the expression of triggering receptor expressed on myeloid cells 2(TREM2)in high-glucose microglia and to investigate the role of TREM2 in the proliferation,migration and phagocytosis of high-glucose microglia.Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose,24 h).The microglia cells were counted and the expression of Iba1 and TREM2 was de-tected.TREM2 siRNA was transfected to detect the proliferation and migration of microglia.The amyloid β-peptide(Aβ)with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia.Results Compared to normal microglia,the number of microglia significantly decreased after high-glucose treatment(P<0.001),while the ex-pression of TREM2 and Iba1 markedly increased(P<0.001).High glucose and TREM2 did not affect the prolifer-ation of microglia.Compared to the normal group,the migration of microglia significantly decreased after high-glu-cose treatment(P<0.05)and TREM2 did not affect the migration ability of high-glucose microglia.Compared to the normal group,the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P<0.001).Furthermore,TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia(P<0.001).Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treat-ment,which significantly affects phagocytosis of Aβ by microglia.
8.Clinical experience in surgical treatment of T4a thyroid cancer
Zhaohui WANG ; Yibo CHEN ; Yixin SUN ; Guiming FU ; Jiahui WANG ; Jin CHEN ; Chunhua LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):62-68
Objective To analyze the clinical features and surgical treatment strategies of T4a thyroid cancer.Methods We retrospectively analyzed patients with thyroid cancer treated in the Department of Head and Neck Surgery of Sichuan Cancer Hospital from January 2004 to May 2021.A total of 303 cases were included and statistically analyzed for pathological type,invaded organs,surgical approach,survival time,and overall survival rate.The postoperative survival curves of the patients were analyzed using the Kaplan Meier method.Results Of the 303 patients enrolled,53 patients were lost to follow-up,and the 1-year,3-year and 5-year overall survival rates were 98.4%(246/250),97.0%(224/231)and 90.2%(92/102),respectively.Of the 94 patients with recurrent laryngeal nerve invasion only,13 were lost to follow-up,and the 1-year,3-year and 5-year overall survival rates were 100%(81/81),98.7%(77/78)and 97.4%(38/39),respectively.There were 151 patients with invasion of recurrent laryngeal nerve and tracheal/laryngeal/esophageal nerve,31 of them were lost to follow-up,and the 1-year,3-year and 5-year overall survival rates were 96.7%(116/120),95.3%(101/106)and 82.2%(37/45),respectively.According to the survival curve analysis,the group with recurrent laryngeal nerve invasion only had an advantage in overall survival time over the group with recurrent laryngeal nerve and tracheal/laryngeal/esophageal invasion.Conclusion Surgical resection is supposed to be preferred for T4a thyroid cancer if there is a chance of surgery.A reasonable surgical strategy,radical surgery while preserving the vital tissues and organs,and one-stage repair and reconstruction can bring patients a better quality of life and prognosis.
9.Hedysari Radix Polysaccharide Regulates Apoptosis of Smooth Muscle Cells in Gastric Antrum of Rat Model of Diabetic Gastroparesis via IGF-1/PI3K/Akt Signaling Pathway
Linlin MIAO ; Shengfang WAN ; Lei ZHANG ; Rongke LI ; Zhaohui WEI ; Xiaoli ZHU ; Hui AN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):130-139
ObjectiveTo observe the effects of Hedysari Radix polysaccharide on the apoptosis of gastric sinus smooth muscle cells and explore the underlying mechanism via the insulin-like growth factor-1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) pathway in the rat model of diabetic gastroparesis (DGP). MethodSixty-two Wistar male rats were randomized into a blank group (n=12) and a modelling group (n=50). The rat model of DGP was established by small-dose multiple intraperitoneal injections of streptozotocin combined with an irregular high-fat and high-sugar diet for 4 weeks. The modeled rats were randomized into model group, mosapride citrate (1.35 mg·kg-1), and high-, medium-, and low-dose (200, 100, and 50 mg·kg-1, respectively) Hedysari Radix polysaccharide groups. The rats were administrated with corresponding drugs by gavage, and those in the blank and model groups with equal volumes of pure water by gavage once a day for 8 consecutive weeks. The random blood glucose and body mass were measured every 2 weeks, and gastric emptying rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of smooth muscle in gastric antrum, and terminal deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) was employed to detect the apoptosis of smooth muscle cells in the gastric antrum. The expression of IGF-1, phosphorylated (p)-PI3K, and p-Akt in the smooth muscle of gastric sinus tissue was detected by immunohistochemistry. Western blot was employed to determine the protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the smooth muscle of the gastric antrum. ResultCompared with the blank group, the model group showed elevated random blood glucose at all time points (P<0.01), decreased body mass and gastric emptying rate (P<0.01), increased apoptotic index of smooth muscle cells in the gastric antrum (P<0.01), down-regulated protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, and Bcl-2, and up-regulated protein level of Bax (P<0.01). Compared with the model group, the 8 weeks of drug administration lowered the random blood glucose, increased the body mass and gastric emptying rate (P<0.05, P<0.01), decreased the apoptotic index of smooth muscle cells in the gastric antrum (P<0.05, P<0.01), up-regulated the protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, and Bcl-2, and down-regulated the protein level of Bax (P<0.05, P<0.01). Compared with the mosapride citrate group,the administration of low-dose Hedysari Radix polysaccharide for 6 and 8 weeks lowered the random blood glucose and decreased the body mass (P<0.05, P<0.01),low and medium-dose Hedysari Radix polysaccharide decreased the gastric emptying rate and the apoptotic index of smooth muscle cells in the astragaloside low-dose group decreased (P<0.05). The protein levels of IGF-1,p-PI3K/PI3K,p-Akt/Akt and Bcl-2(low dose)were down-regulated and the protein level of Bax was up-regulated by low doses of Hedysari Radix polysaccharide (P<0.05, P<0.01). Compared with high-dose Hedysari Radix polysaccharide, low-dose Hedysari Radix polysaccharide elevated random blood glucose and reduced body mass after 6 and 8 weeks of administration (P<0.05, P<0.01), and the low and medium doses decreased the gastric emptying rate, increased the apoptotic index of smooth muscle cells in the gastric antrum (P<0.05, P<0.01), down-regulated the protein levels of IGF-1, p-PI3K/PI3K, p-Akt/Akt, and Bcl-2, and up-regulated the protein level of Bax (P<0.05, P<0.01). Compared with the medium-dose group,the low-dose group of Hedysari Radix polysaccharide had lower body mass,lower gastric emptying rate in rats,higher apoptotic index of smooth muscle cells in gastric sinus tissue after 6 and 8 weeks of administration (P<0.05, P<0.01), and lower protein expression of IGF-1,p-PI3K/PI3K,p-Akt/Akt. ConclusionHedysari Radix polysaccharide protects the smooth muscle cells in gastric antrum against apoptotic injury and promotes gastric motility by activating the IGF-1/PI3K/Akt signaling pathway, as manifested by the up-regulated expression of IGF-1, p-PI3K, p-Akt, and Bcl-2 and down-regulated expression of Bax.
10.Evaluation of the Effect for National Centralized Drug Procurement Policy of PPIs in 33 Hospitals in Wuhan
Zhijuan LIN ; Li LIU ; Wenjuan HE ; Zhiliang ZHANG ; Zhaohui GUO ; Ping LIU ; Quan LEI ; Ying XU
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1723-1728
OBJECTIVE
To analyze the use status and development trend of proton pump inhibitors(PPIs) in 33 hospitals in Wuhan, Hubei Province after the implementation of the national centralized drug procurement(NCDP) policy, and to provide reference for promoting the subsequent rational use of NCDP drugs and improving related policies.
METHODS
To make statistics and analysis of purchasing amount of PPIs, defined daily dose system(DDDs), defined daily dose consumption(DDDc) and utilization rate of 33 hospitals in Wuhan in 2019 and 2022.
RESULTS
After the implementation of the NCDP policy, the total purchasing amount of PPIs decreased by 53.6%, DDDs decreased by 15.4%, DDDc decreased by 45.2%, and the utilization rate of PPIs injectable dosage forms decreased by 12.6%. After NCDP, the highest growth rate of oral dosage forms was omeprazole(5.7%), followed by rabeprazole(5.0%), while injectable dosage forms showed a significant difference in utilization rate, with a significant decline in NCDP varieties and a significant increase in non-NCDP varieties. The overall NCDP utilization rate of PPIs in Wuhan was 64.9%, with little difference among hospitals of different grades.
CONCLUSION
The NCDP policy achieves the purpose of reducing the drug cost of patients and improving the accessibility of drugs, and is more optimized in the selection of dosage forms, which is in line with the policy expectations overall; but the quantity and price of PPIs in Wuhan decreased after NCDP, and highlighted a certain tendency in the selection of varieties. In the future, we still need to optimize measures to guide clinical priority in the selection of NCDP drugs, to ensure and improve the implementation of NCDP policy.


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