1.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
2.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
3.Improvement effects and mechanism of total secondary ginsenosides on hypertrophic changes in cardiomyocytes
Bin LI ; Jia LI ; Zhongjie YUAN ; Mingjun ZHU ; Shiyang XIE ; Yuan GAO ; Rui YU ; Xinlu WANG
China Pharmacy 2025;36(12):1430-1435
OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides (TSG) on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ (Ang Ⅱ). METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups: control group, AngⅡ group (2 µmol/L), TSG group (7.5 µg/mL), PFK-015 group [6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) inhibitor, 10 nmol/L], and TSG+PFK-015 group (TSG 7.5 µg/mL+PFK-015 10 nmol/L). The surface area, protein synthesis, energy metabolism-related indicators [free fatty acid (FFA), coenzyme A (CoA), acetyl coenzyme A (acetyl-CoA)], and the expressions of glycolysis-related factors [hypoxia-inducible factor 1α (HIF-1α), glucose transporter protein 4 (GLUT-4), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and PFKFB3] in primary cardiomyocytes of each group were measured. RESULTS Compared with the control group, the surface area of primary cardiomyocytes and protein synthesis were significantly increased, the content of FFA, protein and mRNA expressions of HIF-1α, LDHA, PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group, while the contents of CoA and acetyl-CoA, the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated (P<0.05). Compared with the AngⅡ group, both TSG group and PFK-015 group showed significant improvements in these indexes, with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone (P<0.05). CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes, decrease protein synthesis, and inhibit their hypertrophic changes. These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.
4.Survey on the awareness and clinical application of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians
Yuanyuan KONG ; Yujie GUO ; Yujuan GUAN ; Xuan LIANG ; Zhongjie HU ; Xiaobo LU ; Mingqin LU ; Yongfeng YANG ; Meifang HAN ; Hong YOU ; Zhiyun YANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(6):1068-1074
ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. MethodsFrom July 19 to December 31, 2024, a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide, including their awareness and practice based on 18 questions regarding testing and referral, diagnosis and treatment, and follow-up. ResultsAmong all respondents, only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B, with an overall awareness rate of 22.0%. Only 20% — 40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy, while 80% — 100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year, 3 years, and 5 years were 67.5% 57.5% and 47.5%,respectively, showing a trend of gradual reduction, which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians, insufficient awareness of the disease among patients, and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection, diagnosis, treatment, and management” for patients with chronic hepatitis B in healthcare institutions, in order to promote the implementation of the guidelines.
5.Mechanism and clinical research progress of remifentanil in the prevention and treatment of emergence agitation
Na WANG ; Yongbo DUAN ; Zhongjie XIAO ; Yujing SONG ; Wenjun YAN
China Pharmacy 2025;36(15):1947-1952
Emergence agitation (EA) is a common complication after general anesthesia, especially in children and adolescents. Remifentanil, as a short-acting μ-receptor agonist, has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression. This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA. Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network, including regulation of microglial inflammatory pathways, and the modulation of cytokines and chemokines,etc. Clinical studies have shown that remifentanil can significantly shorten the recovery time, reduce the incidence of EA, and further optimize the analgesic effect and recovery quality by combining with other drugs (such as local anesthetics, sedatives, and opioid drugs). Future research should further explore the mechanism of action of remifentanil, optimize clinical treatment strategies, and conduct large- scale clinical trials to standardize the drug use plan, while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.
6.Application of a deep learning-based three-phase CT image models for the automatic segmentation of gross tumor volumes in nasopharyngeal carcinoma
Guorong YAO ; Kai SHEN ; Feng ZHAO ; Siyuan WANG ; Zhongjie LU ; Kejie HUANG ; Senxiang YAN
Chinese Journal of Radiological Medicine and Protection 2024;44(2):111-118
Objective:To investigate the effectiveness and feasibility of a 3D U-Net in conjunction with a three-phase CT image segmentation model in the automatic segmentation of GTVnx and GTVnd in nasopharyngeal carcinoma.Methods:A total of 645 sets of computed tomography (CT) images were retrospectively collected from 215 nasopharyngeal carcinoma cases, including three phases: plain scan (CT), contrast-enhanced CT (CTC), and delayed CT (CTD). The dataset was grouped into a training set consisting of 172 cases and a test set comprising 43 cases using the random number table method. Meanwhile, six experimental groups, A1, A2, A3, A4, B1, and B2, were established. Among them, the former four groups used only CT, only CTC, only CTD, and all three phases, respectively. The B1 and B2 groups used phase fine-tuning CTC models. The Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) served as quantitative evaluation indicators.Results:Compared to only monophasic CT (group A1/A2/A3), triphasic CT (group A4) yielded better result in the automatic segmentation of GTVnd (DSC: 0.67 vs. 0.61, 0.64, 0.64; t = 7.48, 3.27, 4.84, P < 0.01; HD95: 36.45 vs. 79.23, 59.55, 65.17; t = 5.24, 2.99, 3.89, P < 0.01), with statistically significant differences ( P < 0.01). However, triphasic CT (group A4) showed no significant enhancement in the automatic segmentation of GTVnx compared to monophasic CT (group A1/A2/A3) (DSC: 0.73 vs. 0.74, 0.74, 0.73; HD95: 14.17 mm vs. 8.06, 8.11, 8.10 mm), with no statistically significant difference ( P > 0.05). For the automatic segmentation of GTVnd, group B1/B2 showed higher automatic segmentation accuracy compared to group A1 (DSC: 0.63, 0.63 vs. 0.61, t = 4.10, 3.03, P<0.01; HD95: 58.11, 50.31 mm vs. 79.23 mm, t = 2.75, 3.10, P < 0.01). Conclusions:Triphasic CT scanning can improve the automatic segmentation of the GTVnd in nasopharyngeal carcinoma. Additionally, phase fine-tuning models can enhance the automatic segmentation accuracy of the GTVnd on plain CT images.
7.Discussion on Features of Acupuncture and Moxibustion Treatment for Migraine Based on Ancient Books and Documents
Zhongjie CHEN ; Jing HU ; Jin HUO ; Yaping LIU ; Shuhua MA ; Qi GAO ; Shuo CUI ; Jingjing WANG
Journal of Traditional Chinese Medicine 2024;65(10):1063-1067
This paper systematically analyzed the ancient monographs of acupuncture and moxibustion and comprehensive medical books from pre-Qin to 1911, and extracted the data according to the etiology and pathogenesis, treatment principles and methods, acupoint selection, needling and moxibustion, and taboos of needling and moxibustion. The pathogenesis of migraine in ancient books and documents is summarized as "the causes are diverse, and phlegm-dampness is the majority". For treatment, the features include "needling has a sequence, and the root and the branch should be treated separately" and "focusing on tonifying deficiency and drain excess". It is also obtained of the rich ideas of acupoints selection, extensive application records of moxibustion, unique application of bloodletting therapy and clear explanation of acupuncture and moxibustion taboos. All mentioned above is expected to enrich the ideas and methods of modern migraine treatment and improve the clinical effects.
8.Severe subcutaneous hematoma after injection of botulinum toxin into the masseter muscle: a case report and literature review
Kemin YI ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Wenbo LI ; Zhongjie YI ; Zhihua QIAO ; Xiaoting LI ; Naixin XIONG
Chinese Journal of Plastic Surgery 2024;40(6):668-673
The patient was a 29-year-old male with a history of hemophilia for more than 10 years. After 6 hours of botulinum toxin injection into the masseter muscle, the redness and swelling of the right face gradually worsened, accompanied by local pain, and restricted mouth opening, etc. The hematoma was absorbed and the swelling subsided significantly after the infusion of coagulation factor Ⅸ. Such cases of large-scale hematomas after botulinum toxin injection in hemophiliacs is rarely reported. This article summarized the diagnosis and treatment process of this case and combines with literature review to provide clinical experience for diagnosis, treatment and prevention of similar complications.
9.A novel bionic stent for external septal retention in East Asian rhinoplasty
Xiancheng WANG ; Shuyuan WANG ; Xingyu XIANG ; Dandan SONG ; Zidi YU ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Wenbo LI ; Zhongjie YI ; Zhihua QIAO
Chinese Journal of Plastic Surgery 2024;40(7):779-786
Objective:To investigate the application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.
10.Predictive value of C-reactive protein to albumin ratio in diagnosis of Kawasaki disease shock syndrome
Zhongjie AN ; Congying WANG ; Mingming ZHANG ; Xiaohui LI
Chinese Journal of Applied Clinical Pediatrics 2024;39(10):750-756
Objective:To identify the predictive validity of C-reactive protein to albumin ratio (CAR) in the early diagnosis of Kawasaki disease shock syndrome (KDSS).Methods:This was a retrospective case-control study.Children with KDSS hospitalized in the Children′s Hospital, Capital Institute of Pediatrics, from January 2019 to December 2022, were selected as the case group, and children with Kawasaki disease (KD) hospitalized in the same period were selected as the control group.After a 1︰4 propensity score matching (PSM) of age and gender, the demographic characteristics, laboratory and imaging examinations, and other clinical data of all the patients were analyzed and compared between the two groups.Multivariate Logistic regression was used to analyze the possible risk factors of KDSS.The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of risk factors for KDSS.Results:There were 45 KDSS children and 269 KD children included in the study.The KDSS patients were older than the KD patients at the onset [43(19, 51) months vs.24(14, 44) months, Z=2.791, P<0.05].After age- and gender-based PSM, there were 45 children in the KDSS group and 180 children in the KD group.The children with KDSS had a shorter duration of fever [6(4, 6) days vs.6(5, 7) days] and a higher risk of coronary artery lesions [42.22%(19/45) vs.25.56%(46/180)] compared to those with KD ( Z=2.184, χ2=4.868, all P<0.05).Multivariate Logistic regression analysis showed that CAR, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, D-dimer, platelet count, serum sodium and estimated glomerular filtration rate were the independent risk factors for KDSS.The area under the ROC curve for identifying KDSS based on CAR was 0.850.When the cutoff value of CAR was 2.73, the sensitivity and specificity were 77.80% and 81.67%, respectively.After subgroup analysis, each one-unit increment in CAR was associated with a 239.6% increased risk of KDSS in children ≥ 3 years old ( OR=3.396, 95% CI: 2.105-5.479, P<0.05). Conclusions:As one of the independent risk factors for KDSS, CAR has high predictive value for early diagnosis of KDSS.In KD patients ≥ 3 years old, the risk of developing KDSS increases significantly with increased CAR.


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