1.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.
2.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.
3.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.
4.Optimization of water extraction technology of Kaixin granules
Zuomin WU ; Shuxian BAI ; Meng NING ; Yunzhi WANG ; Huifen MA ; Jingyuan DONG ; Zhongjie YANG ; Zhishen XIE ; Zhenqiang ZHANG ; Xiaotao YU
China Pharmacy 2025;36(22):2790-2795
OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, tenuifolin, polygalaxanthone Ⅲ and 3, 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times, extraction duration, and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes, analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently, process optimization and validation were conducted by integrating grey relational analysis (GRA) and back propagation (BP) neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two, extracting 3 times,extracting for 1 h each time; the average comprehensive score of the validation experiment was 91.10 (RSD=0.31%, n=3). The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time, extracting for 1.5 h each time; the average comprehensive score of the validation experiment was 95.89 (RSD=0.73%, n=3). Considering practical production requirements, the optimal water extraction technology was extraction performed three times, with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions, with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.
5.Key questions of translational research on international standards of acupuncture-moxibustion techniques: an example from the WFAS Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting.
Shuo CUI ; Jingjing WANG ; Zhongjie CHEN ; Jin HUO ; Jing HU ; Ziwei SONG ; Yaping LIU ; Wenqian MA ; Qi GAO ; Zhongchao WU
Chinese Acupuncture & Moxibustion 2025;45(8):1159-1165
OBJECTIVE:
To provide the experience and demonstration for the transformation of acupuncture-moxibustion techniques standards from Chinese national standards to international standards.
METHODS:
Questionnaire research, literature research, semi-structured interviews and expert consultation were used.
RESULTS:
The safety of acupuncture-moxibustion techniques was evaluated through literature research, and based on the results of the questionnaire survey, expert interviews, and expert consultation, 11 main bodies and structure of the former Chinese national standard, Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting, were adjusted and optimized in accordance with the requirements of international standard (including the language, normative references, purpose, scope, applicable environment, target population, work team, terms and definitions, general principles and basic requirements, structural elements and text structure, and compilation process); and the first international standard, World Federation of Acupuncture-Moxibustion Societis (WFAS) Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting was formulated to specify the general rules for drafting.
CONCLUSION
The 3 key questions, "international compatibility", "technical operability" and "safety" should be solved technically on the basis of explicit international requirements. It is the core technical issue during transforming the national standards of technical benchmark of acupuncture and moxibustion into international standards.
Moxibustion/methods*
;
Acupuncture Therapy/methods*
;
Humans
;
Translational Research, Biomedical/standards*
;
Surveys and Questionnaires
;
China
;
Benchmarking/standards*
6.Public Database-based Study to Explore the Expression and Role of DDB1 in Lung Adenocarcinoma.
Xinkai ZOU ; Ziyi HE ; Yanfei ZHANG ; Yi HU ; Xiaomin WANG ; Zhongjie WU
Chinese Journal of Lung Cancer 2025;28(4):256-266
BACKGROUND:
Lung adenocarcinoma (LUAD) is the predominant subtype of non-small cell lung cancer (NSCLC). Damage-specific DNA binding protein 1 (DDB1), as a core protein of the CUL4-DDB1 ubiquitin ligase complex, is involved in the regulation of DNA damage repair, epigenetic modification, and cell cycle checkpoint activation. While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported, its expression and role in LUAD remain to be elucidated. This study aims to investigate the expression and role of DDB1 in LUAD.
METHODS:
The expression, clinicopathological features and prognosis of DDB1 in LUAD were analysed using databases such as UALCAN, Kaplan-Meier Plotter and GEPIA; The interaction network and enriched functional pathways were constructed by GeneMANIA and Metascape; the correlation between DDB1 and immune cells by combining with TISIDB infiltration was evaluated, and the clustering results of cell subtypes and the expression of DDB1 in different immune cell subpopulations were analysed by single-cell sequencing; finally, tissue microarrays were used to further verify the expression and prognostic value of DDB1 in LUAD.
RESULTS:
The mRNA and protein expression of DDB1 in LUAD tissues were significantly higher than those in normal tissues (P<0.01), and the high expression correlated with later clinical stage (P<0.001), lymph node metastasis (P<0.001) and poor prognosis (P<0.001). Functional enrichment showed that DDB1 was involved in DNA repair and RNA transcriptional regulation, and TISIDB evaluation revealed that DDB1 was negatively correlated with the expression level of immune cells, suggesting the potential regulation of the immune microenvironment. Single cell analysis showed that DDB1 was mainly expressed in T cells, alveolar macrophages and dendritic cells. Tissue microarrays confirmed that overall survival was shorter in the DDB1 high expression group (P<0.001), and Cox multifactorial analysis showed that DDB1 was an independent predictor of LUAD prognosis.
CONCLUSIONS
DDB1 is highly expressed in LUAD, which is associated with poor prognosis, and is closely related to tumor immune cell infiltration, and is involved in tumourigenesis and development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.
Humans
;
Adenocarcinoma of Lung/immunology*
;
DNA-Binding Proteins/metabolism*
;
Lung Neoplasms/diagnosis*
;
Gene Expression Regulation, Neoplastic
;
Prognosis
;
Male
;
Female
;
Middle Aged
7.Modified superomedial pedicle technique for reduction mammaplasty with inverted T-shaped incision
Kai YANG ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Wenbo LI ; Zhongjie YI ; Hongli ZHAO ; Zhihua QIAO
Chinese Journal of Plastic Surgery 2024;40(5):491-498
Objective:To explore the clinical efficacy of modified superomedial pedicle technique using an inverted T-shaped incision for reduction mammaplasty and mastopexy.Methods:A retrospective analysis was conducted on clinical data of patients who underwent modified superomedial pedicle technique for breast reduction surgery with inverted T-shaped incision between March 2021 and March 2023 at the Department of Plastic and Aesthetic (Burn) Surgery, Second Xiangya Hospital of Central South University. Preoperatively, a handheld Doppler ultrasound blood flow detector was used to detect and mark the exit points of the 2nd to 4th perforating vessels of the internal thoracic artery, and a superomedial pedicle containing at least two perforators was designed based on the perforator locations, with a pedicle width generally about 6 cm. Intraoperatively, the pedicle was rotated superolaterally, moving the nipple-areola complex (NAC) upwards to construct a fuller upper pole of the breast and removing excess skin in the lower fold to form a inverted T-shaped incision. Postoperatively, the blood supply of the NAC, breast morphology, and incidence of complications were observed and followed up. Canfield Mirror 7.1.1 software was utilized to measure pre- and post-operative breast morphology data from lateral photographs at 6 months, including total breast area, maximum breast protrusion, upper pole protrusion, lower pole height, and nipple elevation height. The BREAST-Q questionnaire was used to survey patient satisfaction with breast appearance, psychosocial well-being, sexual well-being, and physical health before surgery and 6-12 months after surgery, with each dimension scoring 0-100 points, where higher scores indicate greater satisfaction and health. SPSS 28.0 software was used for data analysis, with normally distributed measurement data expressed as Mean±SD, and paired t-test was applied for comparisons of pre- and post-operative breast morphology data (the first 4 indicators) and BREAST-Q scores, with P<0.05 considered statistically significant. Results:A total of 56 female patients were included, with an age of (32.0±6.7) years and a body mass index of (29.1±5.7) kg/m 2. Preoperative Doppler ultrasound blood flow detection showed that none of the patients had missing or significantly variant perforators of the superomedial pedicle. The volume of breast tissue removed ranged from 890 to 1 800 ml, averaging 1 250 ml, with an average pedicle width of 5.4 cm (4.0-7.0 cm). The follow-up period was (13.3±2.5) months, during which all patients exhibited good blood supply to the NAC and favorable breast morphology, with universal high satisfaction with surgical outcomes. Postoperatively, one case developed incisional seroma, which resolved naturally within 3 months; two cases experienced minor incision dehiscence, which healed well after dressing changes; all other patients recovered well without any complications such as flap necrosis or hematoma. Comparison of breast morphology data showed significant reductions in postoperative left and right total breast area ( P<0.05 for both), and increases in maximum breast protrusion and lower pole height postoperatively ( P<0.05 for both), while the difference in upper pole protrusion was not statistically significant ( P>0.05 for both); postoperative left and right nipple elevation heights were (6.30±1.84) cm and (6.52±1.66) cm, respectively. Among the 44 patients who completed the BREAST-Q survey both before and after surgery, scores showed significant improvements in postoperative breast satisfaction [(50.30±10.30) points vs. (83.20±6.02) points] ( t=5.17, P=0.008) and psychosocial well-being [(56.20±17.20) points vs. (89.70±2.70) points] ( t=5.09, P=0.010), while sexual well-being and physical health scores did not differ significantly from preoperative scores ( P>0.05 for both). Conclusion:Preoperative identification of perforator locations using a handheld Doppler blood vessel detector, followed by the design of a modified superomedial pedicle technique for reduction mammaplasty with inverted T-shaped incision, can not only ensure NAC blood supply, avoiding ischemic necrosis due to vascular anomalies, but also maximally reduce pedicle width and increase pedicle rotation flexibility, achieving desirable breast shaping 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.Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells
NAN FULONG ; NAN WENLONG ; YAN XIN ; WANG HUI ; JIANG SHASHA ; ZHANG SHUYUN ; YU ZHONGJIE ; ZHANG XIANJUAN ; LIU FENGJUN ; LI JUN ; ZHOU XIAOQIONG ; NIU DELEI ; LI YIQUAN ; WANG WEI ; SHI NING ; JIN NINGYI ; XIE CHANGZHAN ; CUI XIAONI ; ZHANG HE ; WANG BIN ; LU HUIJUN
Journal of Zhejiang University. Science. B 2024;25(3):254-270,后插1-后插4
As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.


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