Objective To investigate the inhibitory effects of docosahexaenoic acid (DHA)and 5-fluorouracil (5-FU)in combination on human gastric cancer cell line AGS in vitro .Methods Human gastric cancer line AGS was treated with different concentrations of DHA and 5-FU alone or in combination.The inhibition of cell proliferation was evaluated by MTT assay.Dose of median (IC50 )of drugs (alone or in combination)and the combination index (CI)were calculated using the median-effect equation and the combination index equation of Chou-Talalay.Flow cytometry was used to detect the cell cycle distribution.The expression of mitochondrial respiratory membrane protein complex in AGS cells was analyzed with Western blot.Results DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS in significantly time-dependent and dose-dependent manners (P <0.05).IC50 values with DHA or 5-FU administered for 24 h and 48 h were 5 1.60 μg/mL (DHA:24 h),34.82 μg/mL (DHA:48 h),45.90 μg/mL (5-FU:24 h),and 1 6.86 μg/mL (5-FU:48 h), respectively.DHA remarkably strengthened the inhibitory effect of 5-FU and decreased IC50 of 5-FU by 3.56 -2.1 5 folds.The combination of DHA and 5-FU showed synergism.Flow cytometry showed that AGS cells treated with DHA and 5-FU were arrested in G0/G1 phase and the proportion of AGS cells in G0/G1 phase increased compared with that in the control group,DHA group and 5-FU group,while the proportion of the cells in S phase decreased significantly (P < 0.05 ).Western blot showed after treatment with DHA and 5-FU for 48 h,the expression of mitochondrial respiratory membrane protein complex was significantly decreased compared with control group,DHA group and 5-FU group (P <0.05).Conclusion DHA could act synergistically with 5-FU in inhibiting the growth of gastric carcinoma cells,and meanwhile decrease the dose of 5-FU.The mechanism may be associated with cell cycle arrest in G0/G1 phase and interference in the energy metabolism of AGS cells due to inhibition of the expression of mitochondrial oxidative respiratory chain complexes by the two compounds.

Objective To investigate the effects of different concentrations of isoflurane on viability in rat primary cortical neurons. Methods Primary cortical neurons were isolated from neonatal Wistar rats (less than 24 h after birth) and exposed to 0.6 %, 1.2 % and 2.4 % isoflurane for 1, 2, 4, 8, 12 or 24 h, cell viability was evaluated by MTT reduction and LDH release assays. Changes in intracellular [Ca2+]i were detected by real-time confocal microscopy after the neurons were exposed to different concentrations of isoflurane. Results Exposure to 0.6% isoflurane for 24 h significantly increased viability of the primary rat cortical neurons as shown by decrease in LDH release and increase in MTT and elevation of peak [Ca2+]i. Exposure to 1.2% isoflurane for 12 or 24 h and to 2.4% isoflurane for 8, 12 or 24 h significantly reduced viability of cortical neurons associated with high and fast elevation of peak [Ca2 +] i. Conclusion Exposure to 0.6 % isoflurane increases viability of the primary rat cortical neurons. Exposure to 1.2% isoflurane and to 2.4% isoflurane decreases cell viability and the mechanism may be related to the changes in calcium concentrations in the neurons.

ABSTRACT:Objective To investigate the effects of ω-3 polyunsaturated fatty acids on the proliferation of human gastric cancer cell line AGS and the possible mechanisms.Methods Human gastric cancer line AGS and human microvascular epithelial cell HMEC-1 were treated with different concentrations of docosdhexaenoic acid (DHA)and eicosapentaenoic acid (EPA).The inhibition of cell proliferation was evaluated by MTT assay and cell morphology.Flow cytometry was used to detect the cell cycle change.The expressions of mitochondrial respiratory membrane protein complex Ⅰ,Ⅱ and V were analyzed with Western blot.Results DHA and EPA could markedly inhibit the proliferation of AGS in significant time-dependent and concentration-dependent manners (P < 0.05 ). The inhibitory effect of DHA was stronger than that of EPA under the same concentration gradient (P <0.05).The morphological changes of cells were characterized by cell shrinkage and weak adhesion.Flow cytometry showed that AGS cells treated with DHA and EPA were arrested in G0/G1 phase and the proportion of AGS cells in G0/G1 phase increased compared with that of the control group while the proportion of the cells in S phase decreased significantly (P <0.05).Western blot showed after treatment with DHA for 24 h and 48 h,compared with control group,the expressions of mitochondrial respiratory membrane protein complex Ⅰ,Ⅱ and Ⅴ were obviously decreased.The longer effect of DHA,the lower expression of membrane protein complex (P <0.05).DHA had little effect on cell proliferation,morphology or mitochondrial membrane protein complex in HMEC-1 (P >0.05).Conclusion ω-3 PUFAs can selectively inhibit the growth and proliferation of human gastric cancer cell line AGS.These effects may be as-sociated with arresting cell cycle in G0/G1 phase and inhibiting the energy metabolism of AGS cells.

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.

Post-traumatic tetanus is the main type of non-neonatal tetanus. To reduce the incidence and mortality rate of tetanus and guide the primary medical institutions to prevent and control tetanus after trauma, National Immunization Planning Technical Working Group of the Chinese Center for Disease Control and Prevention has compiled this document in the reference with Position Paper by World Health Organization, the latest research progress from home and abroad. The guidelines focus on the basic procedures for the prevention and disposition of post-traumatic tetanus, the application of tetanus vaccines and immune preparation, and the pre-exposure immunization in high-risk populations of trauma.

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate remains 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.