Purpose:To evaluate the feasibility of dose escalation in non small cell lung cancer(NSCLC) treatment using 3 dimensional conformal radiotherapy and to assess the immediate responses and acute side effects.Methods:25 patients with inoperable NSCLC were evaluated from October 2000 to July 2001. Conventional irradiation technique was used until the tumor dose reached 40 41.4Gy. FOCUS2.6.1 of CMS three dimensional treatment planning system(3D TPS) was used to design the dose escalation treatment plan and DVHs was used to optimize it.The planning target volume (PTV)encompassed 1 1.5cm outside the clinical target volume(CTV).The irradiation doses of dose escalation treatment plan ranged from 25Gy to 30Gy,and were delivered in daily fractions of 2.5 3 Gy,5 days a week. WHO criteria and RTOG/EORTC grading scheme were used to assess the immediate responses and acute side effects.Results:All 25 patients completed the treatment successfully. The median radiation dose to the gross tumor volume(GTV) was 7012cGy(62 45 Gy 71 40 Gy).The overall immediate response rate (CR+PR)was 72.0%(18/25). According to the RTOG grading scheme , acute radiation esophagitis occurred in 24.0%(6/25)of patients with Grade 1 2 and 4.0%(1/25)with Grade 3 respectively. Acute radiation pneumonitis occurred in 16.0%(4/25)of patients with Grade 1 2 and 4.0%(1/25)with Grade3 respectively. The bone marrow toxicity occurred in 16.0%(4/25)with Grade 1 2. Damage to the heart occurred in 12.0%(3/25) with grade1 2. Median follow up is 14 months.Conclusions:Dose escalation in NSCLC treatment using 3 dimensional conformal radiotherapy has an encouraging immediate response rate with lower acute complication. Late side effects of irradiated and survival will be observed. [

Glaucoma is an irreversible blinding eye disease caused by the structural and functional damage of optic nerve induced by pathological increase of intraocular pressure (IOP), characterized by multiple causes and strong heterogeneity.The control of IOP to reduce the risk of optic damage has been the main therapeutic strategy of glaucoma for many years.However, in clinical experience, some patients show progress of optic nerve damage despite the effectively controlled IOP, the mechanism of non-IOP-dependent secondary damage is still an urgent problem to be solved and a research hotspot in the pathogenesis of glaucoma.With the continuous innovation of molecular biological technology, breakthroughs have been made in the field of basic research.Partial visual recovery can be boosted by alleviating local immune and inflammatory responses.Due to a lack of symbolic clinical application results, it has become an immediate priority to attach importance to the combination of basic clinical research and facilitate the transformation of results.Starting from the theory of glaucoma-immune inflammation, understanding the importance of the immune homeostasis of eyes, paying close attention to the linkage of eyes and brain in physiopathological process and the progression of diseases in the whole visual pathway, and fully understanding and effectively making good use of the opportunities and implications brought by new techniques will have significant effect in formulating clinical diagnosis and treatment plans.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins