OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

The leukocyte immunoglobulin-like receptor LILRB4(ILT3 or CD85k),a member of the immunosuppressive re-ceptor family,is expressed predominantly on the cell membranes of immune cells of myeloid origin,and exerts an immunosuppressive effect in immune regulation by activating either the autoinhibitory motif(ITIM)or by inhibiting Fc receptor activation motif(ITAM).In tumors,activation of LILRB4 receptor generates an immunosuppressive tumor microenvironment that assists in tumor invasion and metastasis,and in inflammatory diseases,LILRB4 is expressed on a variety of cells,such as monocytes,macrophages,mast cells,etc.,and attenuates inflammatory responses.Currently,LILRB4 has become a therapeutic target for tumors and various inflammatory diseases,and anti-LILRB4 monoclonal antibodies against acute myeloid leukemia(AML)have entered clinical trials.This review dis-cusses LILRB4 in terms of its structural distribution,signaling,therapeutic targets,and new drug development.

OBJECTIVE To explore the improvement mechanism of Modified sanhuang ointment on anal ulcers and swelling model rats. METHODS The anal ulcer model of the rat was induced by using glacial acetic acid； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on body weight， area of anal ulcer， grade of anal ulcer were investigated. The other groups of rats were used to induce rectal swelling models with croton oil； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on the rate of rectal and anal swelling， serum contents of inflammatory factors [interleukin 2 （IL-2）， IL-4， tumor necrosis factor （TNF-α）]， pathological morphology of rectal tissue， the expression of transient receptor potential channel V1 （TRPV1） and substance P in rectal tissue and rectal vascular permeability were investigated. RESULTS In Modified sanhuang ointment， the increase in body weight was enhanced， and the area of anal ulcers， as well as the grade of anal ulcers in rats with anal ulcer models， were reduced to varying degrees； rectal tissue damage in rectal swelling model rats was improved； the rate of rectal and anal swelling， the serum contents of inflammatory factors， the expressions of TRPV1 and substance P in rectal tissue， and rectal vascular permeability were all decreased （P＜0.05 or P＜0.01）. The effect of Modified sanhuang ointment was better than that of western medicine positive control and TCM positive control.Modified sanhuang ointment can improve anal ulcers and swelling in rats by reducing the release of inflammatory factors， inhibiting the expression of TRPV1 and substance P.

Objective To investigate the incidence, clinical symptoms, correlative risk factors and prognosis of dysautonomia in patients with severe traumatic brain injury. Methods A total of 142patients with severe traumatic brain injury treated from January 2008 to March 2010 were retrospectively surveyed to compare the clinical features of dysautonomia group and control group. Logistic regression was used to analyze the risk factors for dysautonomia. At 6 months post-trauma, the Glasgow Outcome Score (GOS) was used to measure the outcome. Results Of all the patients, 94 patients survived and were followed up. There were 16 patients ( 17% ) diagnosed as dysautonomia depended on clinical symptoms,with statistical difference in aspects of GCS, coma duration, ICU time and average length of stay (ALOS)(P < 0.05). The patients with dysautonomia tended to have poorer outcome ( P < 0.05 ) and showed a positive association with diffuse axonal injury (DAI) ( OR = 11. 25, CI 7.65-16.54 ). Conclusion Dysautonomia has high incidence and is usually severe in patients with severe traumatic brain injury,when DAI may contribute to its occurrence and result in poor prognosis.

This study examined the effects of ω-3 polyunsaturated fatty acid (ω-3PUFA) on the expression of toll-like receptor 2 (TLR2),toll-like receptor 4 (TLR4) and some related inflammatory factors in peripheral blood mononuclear cells (PBMCs) of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital (Wuhan,China) between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score (ISS) no less than 16,were enrolled in the study and divided into two groups at random (n=16 in each):ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission (day 0),and 1,3,5 and 7days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support (both P＜0.05).The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day (P＜0.05 for all).It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.

This study examined the effects of ω-3 polyunsaturated fatty acid (ω-3PUFA) on the expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and some related inflammatory factors in peripheral blood mononuclear cells (PBMCs) of patients with early-stage severe multiple trauma. Thirty-two patients who were admitted to the Department of Traumatic Surgery, Tongji Hospital (Wuhan, China) between May 2010 and November 2010, and diagnosed as having severe multiple trauma with a injury severity score (ISS) no less than 16, were enrolled in the study and divided into two groups at random (n=16 in each): ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days. Peripheral blood from these patients was collected within 2 h of admission (day 0), and 1, 3, 5 and 7 days after the nutritional support. PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively, the levels of NF-κB by quantum dots-based immunofluorescence assay, the levels of TNF-α, IL-2, IL-6 and COX-2 by ELISA, respectively. The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support (both P<0.05). The levels of TNF-α, IL-2, IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day (P<0.05 for all). It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2, TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma, which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.

Objective To explore the PGI 2 and TXA 2 for lung cancer patients and ones with lung cancer metastasis,in onder to provide nomal index for diagnosis and differential diagnosis in lung cancer metastasis.Methods To test plasma PGI 2 and TXA 2 by means of RIA in all cases.One group of patients who received non operative treatment:Six cases of patients with distant metastasis;Eight cases with hilus of long metastasis;Seven cases without metastasis.The other group of patients who received radical operation;Six cases of patients with distant metastasis;Seven cases with hilus of lung metastasis;Six cases without metastasis.Result The PGI 2/TXA 2 ratio of the patient whether distant metastasis or hilus of lung metastasis was obviously lower than that of the patients without metastasis( P