BACKGROUND: Cervical sympathetic ganglia block accelerates the re covery of the homeostasis of organic nervous-endocrine-immune system, butit is still unclear whether it can suppress the imbalance of homeostasis in duced by post-traumatic stress disorder. OBJECTIVE: To observe the effect of cervical sympathetic ganglia blockon the mortality of mice with combined radiation and burn injury, andwhether it can become an easy and effective method to treat secondarydamage after serious trauma. DESIGN: A randomized grouping design, an animal controlled experiment. SETTING: Department of Anesthesiology, Guangzhou General Hospital, Guangzhou Military Area Command of Chinese PLA.MATERIALS: The experiments were carried out in the Institute of Combined Injury, the Third Military Medical University of Chinese PLA between February 2004 and July 2005. Totally 160 Kunming mice were randomly divided into control group (n=50) and cervical sympathetic ganglia block group (n=50). In the control group, the mice were only induced to models of combined radiation and bum injury, and treated with injection of 0.3 mL saline at cervical part. In the cervical sympathetic ganglia block group, the mice were induced to models of combined radiation and burn injury, and then treated with cervical sympathetic ganglia block, once a day for 14 days continuously.METHODS: Methods to induce injury in the animals: ① Radiation injury: The mice were given even radiation of 60Coγ ray (5 Gy) at a distance of 1.5 m to the whole body, the rate of absorptive dosage was (5.17-5.33) mGy/s. ② Burn injury: After the radiation injury, coagulated gasoline was smeared on the back and burnt for 8 s to induce degree Ⅲ burn injury of 15% of the total body surface, which was proved by the pathological section. Methods of cervical sympathetic ganglia block: Cervical sympathetic ganglia block was given bilaterally, and then the mice were injected with 0.2 mL lidocaine (5 g/L), and it was observed whether the symptoms similar to Horner syndrome (hyperemia of conjunctiva, drooping eyelid,blushing, smaller eyeslit) occurred or not at 5 minutes after injection.MAIN OUTCOME MEASURES: The mortality at 2, 5, 7, 10, 20 and30 days after injury and the changes of the numbers of red blood cells,white blood cells and blood platelet in peripheral blood at 7, 14 and 21 days after injury were observed in both groups. The effects of cervical sympathetic ganglia block on the levels of tumor necrosis factor-alpha (TNF-α),interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum at 3, 6 and 14days after combined radiation and burn injury were also observed.RESULTS: All the 160 mice were involved in the analysis of results without deletion. ① Compared with the control group, the mortalities at 5,7, 10, 15, 20 and 30 days in the cervical sympathetic ganglia block group were significantly decreased [control group: 8%, 22%, 32%, 54%, 74%,82%, 90%; cervical sympathetic ganglia block group: 8%, 14%, 16%, 22%,28%, 34%, 56%]. ② Compared with the control group, the numbers of red blood cells, white blood cells and blood platelets in peripheral blood at 7,14 and 21 days after injury in the cervical sympathetic ganglia block group were significantly increased [at 21 days: red blood cells: 23.21×1012 L-1, 14.58×1012 L-1; blood platelet: 16.87×1011 L-1, 12.57×1011 L-1; white blood cells: 20.65×109 L-1, 14.58×109 L-1]. ③ The levels of TNF-α, IL-1β andIL-6 in serum at 3, 6 and 14 days after injury in the cervical sympathetic ganglia block group were significantly decreased as compared with those in the control group [at 14 days: TNF-α: 189, 365 ng/L; IL-1β: 14, 23 ng/L;IL-6: 70, 132 ng/L].CONCLUSION: Cervical sympathetic ganglia block can significantly decrease the mortality of animals with combined radiation and burn injury,and it is an easy and effective method to treat serious trauma, and the mechanism may be realized through accelerating the recovery of hematopoietic function and suppressing the excessive inflammatory reaction.

Objective:To construct the yeast expressive vector of rmFⅦ, in which mFⅦ was mutated to inhibit coagulation without affecting the affinity for TF, and express it in Pichia pastoris. Methods:The full length cDNA encoding mFⅦ was amplified from a mouse liver by RT-PCR method, site-direct mutated and restriction enzyme digested as design. Cloning into pPIC9K, electroporation of Gs115, in vivo screen of multiple inserts by G418 resistance, BMGY/BMMY are used for induction and expression of rmFⅦ in pichia pastoris. These proteins were also screened for functional activity. Results: Three different rmFⅦ-pPIC9K yeast expression vectors and it's aim protein were obtained,two kinds of proteins were found to be functional active as design. Conclusion:rmFⅦ protein can be expressed in pichia pastoris and it might facilitate the development of tumor-target molecule, and novel anti-agiogenesis drug study.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*