1.Luoshi Neiyi Prescription Treats Endometriosis Through TLR4/NF-κB Signaling Pathway
Yuanyuan RUAN ; Sai XU ; Jiangyue TANG ; Xiang LI ; You ZOU ; Fangli PEI ; Lizheng WU ; Kaidi ZHENG ; Shuhong LIN ; Weilan ZHONG ; Cheng ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):185-196
ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis (EMs) through the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats, which were randomized into a sham operation group (10 rats) and a modeling group (40 rats). An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups (n=9 each): The model group, the low-dose (7.87 g·kg-1) Luoshi Neiyi prescription group, the high-dose (15.74 g·kg-1) Luoshi Neiyi prescription group, and the dienogest (0.20 mg·kg-1) group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin (HE) staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of inflammatory factors including interleukin-1β (IL-1β) and prostaglandin E2 (PGE2) in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor A (VEGFA) in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4, myeloid differentiation factor 88 (MyD88), phosphorylated nuclear factor-κB (p-NF-κB)/NF-κB, MMP-9, and VEGFA in the eutopic endometrial tissue. In the cell experiments, the cell-counting kit-8 (CCK-8) assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum, and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum, resatorvid (TAK-242, a TLR4 inhibitor), and lipopolysaccharides (LPS, a TLR4 agonist) were conducted, and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group, the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score (P<0.01). Furthermore, HE staining revealed the model group exhibited a thickened eutopic epithelium, stromal cell disarrangement, and evident infiltration of inflammatory cells. In addition, the model group showed elevated serum levels of IL-1β and PGE2 (P<0.05, P<0.01), increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue (P<0.01), and up-regulated protein levels of TLR4, MyD88, p-NF-κB/NF-κB, MMP-9, and VEGFA in the ectopic endometrial tissue (P<0.05, P<0.01). Compared with the model group, all treatment groups exhibited a reduction in the ectopic lesion volume (P<0.01). Furthermore, the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group (P<0.05, P<0.01). The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE2 levels, and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE2 levels in EMs rats (P<0.05, P<0.01). The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue (P<0.05, P<0.01) and down-regulated protein levels of TLR4, MyD88, p-NF-κB/NF-κB, MMP-9, and VEGFA in the ectopic endometrial tissue (P<0.05, P<0.01). The cell experiments showed that 5%, 10%, and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group, 5%, 10%, and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4, MyD88, p-NF-κB/NF-κB, MMP-9, and VEGFA (P<0.01). Compared with the control group, the LPS group showed increased expression of the above proteins (P<0.01). Compared with the LPS group, the LPS+5%, 10%, and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins (P<0.05, P<0.01). ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive, invasive, and angiogenic biological processes in the ectopic endometrial tissue, thereby exerting its therapeutic effect on EMs.
2.Controlled decompression under intracranial pressure monitoring in craniotomy of patients with severe cerebral hemorrhage
Zhenhai FEI ; Jianguo YANG ; Xingming ZHONG ; Yiqi WANG ; Zhaohui ZHAO ; Yong CAI ; Lei ZHANG ; Hua GU ; Tao YANG ; Weilan LIU ; Kankai TANG ; Zhidong CHEN
Chinese Journal of Neuromedicine 2019;18(5):494-500
Objective To explore the value of controlled decompression under intracranial pressure monitoring in craniotomy of patients with severe cerebral hemorrhage.Methods One hundred and six patients with severe cerebral hemorrhage,admitted to our hospital from January 2015 to July 2018,were prospectively enrolled.These patients were divided into control group (n=5 l) and treatment group (n=55) according to their families' wishes.The patients in the control group were treated with traditional craniotomy and hematoma removal;the patients in the treatment group were treated with controlled decompression combined with craniotomy and hematoma clearance under intracranial pressure monitoring,and intracranial pressure monitoring and management were carried out after operation.The rate of bone flap acceptance during operation,incidences of complications such as re-bleeding,scalp exudation,intracranial infection and cerebral infarction after operation,rate of re-operation and Glasgow outcome scale scores 6 months after injury were compared and analyzed between the two groups.Results Five patients had midway withdrawal (2 from the control group and 3 from the treatment group),and 101 patients (49 from the control group and 52 from the treatment group) were included in the statistical analysis.The rate of bone flap acceptance in the treatment group (69.2%) was significantly higher than that in the control group (24.5%,P<0.05).The incidences of complications such as bleeding,scalp exudation,intracranial infection and cerebral infarction (11.5%,7.7%,3.8%,and 13.5%) were significantly lower than those in the control group (30.6%,22.4%,16.3%,and 34.7%,P<0.05).The re-operation rate (3.8%) was significantly lower than that in the control group (16.3%,P<0.05).Good recovery rate in the treatment group (76.9%) was significantly higher than that in the control group (55.1%,P<0.05).The mortality rate (7.7%) was significantly lower than that of the control group (22.4%,P<0.05).Conclusion For patients with severe cerebral hemorrhage,controlled decompression under intracranial pressure monitoring combined with craniotomy and hematoma removal can significantly improve the rate of bone flap acceptance,reduce the rate of second-stage cranioplasty,reduce the incidence of complications and re-operation rate,and more effectively improve the quality of life and prognosis of patients.
3.Improved antitumor efficacy by combinationtreatment with recombined VEGF protein vaccineand cyclophosphamide in H22 hepatocellular carcinoma bearing-mice
Chunfeng SI ; Meiyu LU ; Qiaoyun WANG ; Weilan ZHONG ; Ling ZHOU ; Xiaoping YANG ; Maolei XU
Chinese Pharmacological Bulletin 2017;33(5):617-621
Aim To investigate the antitumor and antiangiogenic effects of combined low-dose cyclophosphamide(CTX)and recombined VEGF protein vaccine.Methods In this experiment,H22 hepatocellular carcinoma model was established in BALB/c mice.Mice were randomly divided into four groups: control group,CTX group(CTX),VEGF protein vaccine group(V2)and CTX plus V2 group(CTX+V2).The anti-tumor efficacy and antiangiogenic effect were investigated using a subcutaneous tumor model and an intradermal tumor model.Western blot and ELISAwere further adopted to detect the specific anti-VEGF antibody.Results CTX+V2 group displayed a lower tumor volume and tumor weight than either the single therapy group in the subcutaneous tumor model(P<005 vs V2,P<001 vs CTX).Meanwhile,CTX+V2 was more effective for antagonizing tumor-associated angiogenesis compared with either the single therapy(P<005 vs V2,P<001 vs CTX).After CTX+V2 immunization,high titer of anti-VEGF antibody was detected by ELISA and verified by Western blot.Conclusion The therapy of CTX combined with V2 has significant synergistic effect against H22 hepatocellular carcinoma.

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