1.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
2.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
3.Current Situation, Problems and Countermeasures of Experimental Research on Traditional Chinese Medicine Regulating PI3K/Akt Signaling Pathway in Rats with Polycystic Ovary Syndrome
Pengxuan YAN ; Yiqing LIU ; Nanxing XIAN ; Linjing PENG ; Kun LI ; Jingchun ZHANG ; Yukun ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):259-266
Polycystic ovary syndrome(PCOS) and its resulting infertility is one of the common diseases of gynecology and reproductive endocrinology. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway is relatively well-studied in the development of intervention in PCOS, and the experiments on PCOS in rats conducted by traditional Chinese medicine through this signaling pathway is also the main direction of mechanistic research. In this paper, 20 articles published in academic journals in the past 5 years were selected through the corresponding criteria, and the objective situation and existing problems of the selected research projects were analyzed from five aspects, namely, baseline data, modeling and treatment, grouping, evaluative indexes, and pharmacodynamic indexes. It is found that there were different degrees of problems in each research project, such as the observation indicators of modeling, criteria for judging the success of the model, the treatment period, the calculation of dosage of prescription/active ingredients and specific dosage were not clearly defined, which could easily lead the bias of the results or reduce the validity of experimental data. Based on this, the list of PCOS rat experimental research operations was formed, involving five categories of experimental rats, model construction, study implementation, outcome measures and analysis and report with a total of 21 operation lists, with a view to provide a reference for the subsequent PCOS experiments related to scientific research and helping to form high-quality results.
4.Discussion on the Application of Warm-Yang Method in Polycystic Ovary Syndrome Infertility
Pengxuan YAN ; Haiyan ZHANG ; Yukun ZHAO ; Yabei GAO ; Kun LI ; Jingchun ZHANG ; Yuping ZHAO ; Zixiao WEI
Journal of Traditional Chinese Medicine 2025;66(3):312-316
It is believed that there is a pathogenesis of yang deficiency in polycystic ovary syndrome (PCOS) infertility, and it is concluded that warm-yang method has a better effect in improving endometrial abnormality, enhancing the quality of follicles, correcting endocrine disorders, and resolving or alleviating clinical symptoms in PCOS infertility. Based on Yanghe Decoction (阳和汤), a representative traditional Chinese medicine decoction for warming yang, Yanghe Xiaonang Decoction (阳和消囊汤) was formulated, combining with warm medicinals according to symptoms, and aerobic exercise was also advocated to help generate and develop yang qi, in order to provide ideas for clinical treatments.
5.Effect Mechanism of Guizhi Fulingwan in Regulating Sex Hormone Disorders in Rats with Benign Prostatic Hyperplasia Based on Serum Metabolomics
Chengchen LI ; Yuanpeng HUANG ; Qian ZHANG ; Dian ZENG ; Lingang KONG ; Yukun FAN ; Yuanduo XIA ; Hao CHEN ; Feng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):21-29
ObjectiveTo analyse the efficacy and mechanism of Guizhi Fulingwan in regulating sex hormone disorders in rats with benign prostatic hyperplasia (BPH). MethodsThirty male SD rats were randomly divided into a sham group, a model group, a finasteride group (0.45 mg·kg-1·d-1), and low-dose and high-dose groups of Guizhi Fulingwan (0.135, 0.337 5 g∙kg-1∙d-1), with six in each group. The BPH model was prepared by subcutaneous injection of 3.5 mg∙kg-1∙d-1 testosterone propionate after debridement surgery in all groups except the sham group. The rats in the sham group and the model group were administered with an equal volume of saline by gavage, and the rest of the groups were administered with the corresponding medicinal solution by gavage for 35 days. Histopathology in rats was evaluated by prostate wet weight, volume, index, and hematoxylin-eosin (HE) staining. The serum sex hormone levels of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) were determined by enzyme-linked immunosorbent assay. The protein expression of the androgen receptor (AR) was detected by immunohistochemistry. The serum metabolism profiles of rats in the sham group, the model group, and the high-dose group of Guizhi Fulingwan were compared by ultra-high performance liquid chromatography tandem Fourier transform mass spectrometry (UHPLCQ Exactive) to screen for metabolic markers and to obtain relevant metabolic pathways. ResultsCompared with those in the sham group, the wet weight, volume, index, serum sex hormone level, and AR protein expression of the prostate in the model group were all elevated (P<0.05, P<0.01), and the histomorphology showed pathological changes. Compared with those in the model group, the wet weight, volume, index, serum sex hormone level, and AR protein expression of the prostate in the intervention groups showed a decreasing trend (P<0.05, P<0.01), and histopathology was improved. Serum metabolomics analysis obtained a total of 40 metabolic markers related to the intervention effect of Guizhi Fulingwan, such as dehydrosafynol, hyoscyamine, and lumichrome, which were involved in the pathways of autophagy, riboflavin metabolism, and retrograde endocannabinoid signaling. ConclusionGuizhi Fulingwan can effectively regulate sex hormone disorders in BPH rats, and its mechanism may be related to autophagy, riboflavin metabolism, and retrograde endocannabinoid signaling.
6.Progress of contrast-enhanced ultrasound in evaluating renal cortical perfusion
Ping ZHAO ; Ying ZHANG ; Yukun LUO
Chinese Journal of Geriatrics 2024;43(7):781-784
The occurrence, progression, and prognosis of renal diseases are closely linked to renal blood perfusion.Accurate evaluation of renal perfusion is essential for clinical assessment of kidney function.Unlike CT and MRI, contrast-enhanced ultrasound(CEUS)is a non-invasive, convenient, real-time imaging technique that enables quantitative assessment of renal cortical perfusion, providing microcirculation information for clinical diagnosis.This review article discusses the clinical relevance of CEUS in evaluating renal cortical perfusion status.
7.Retroperitoneal laparoscopic surgery of pediatric calyceal diverticulum: 2 cases report
Xinyan WANG ; Xin WANG ; Yong WU ; Dongzheng ZHANG ; Xiong MA ; Cong WANG ; Zhenhua ZHANG ; Yukun MA ; Baolong WEI ; Yong GUAN
Chinese Journal of Urology 2024;45(5):393-394
Pediatric calyceal diverticulum (CD) is a relatively rare entity. Fewer cases were reported in China treated by retroperitoneal laparoscoopic surgery in children. In this paper, 2 cases of children with CD admitted to our hospital were reported. CT urography showed cystic low-density mass without obvious enhancement, and delayed contrast agent was found to enter the lesion. Both cases underwent cystoscopy + retroperitoneoscopy + diverticular neck suture. They were followed up for 15 months and 9 months after the surgery, respectively, with favorable outcomes and no recurrence of CD.
8.The Circular RNA Circ_0043947 Promoted Gastric Cancer Progression by Sponging miR-384 to Regulate CREB1 Expression
Chongxin ZHANG ; Fan ZHANG ; Yukun LI ; Pengfei YANG ; Yang LIU ; Wenxiao YANG
Gut and Liver 2024;18(6):977-991
Background/Aims:
The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC.
Methods:
The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model.
Results:
Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo.
Conclusions
Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.
9.The Circular RNA Circ_0043947 Promoted Gastric Cancer Progression by Sponging miR-384 to Regulate CREB1 Expression
Chongxin ZHANG ; Fan ZHANG ; Yukun LI ; Pengfei YANG ; Yang LIU ; Wenxiao YANG
Gut and Liver 2024;18(6):977-991
Background/Aims:
The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC.
Methods:
The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model.
Results:
Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo.
Conclusions
Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.
10.The Circular RNA Circ_0043947 Promoted Gastric Cancer Progression by Sponging miR-384 to Regulate CREB1 Expression
Chongxin ZHANG ; Fan ZHANG ; Yukun LI ; Pengfei YANG ; Yang LIU ; Wenxiao YANG
Gut and Liver 2024;18(6):977-991
Background/Aims:
The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC.
Methods:
The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model.
Results:
Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo.
Conclusions
Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.

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