Objective To investigate the curative effect and safety of percutaneous intradiscal injection of ozone combined with epidural injection of collagenase for the treatment of prominent lumbar disc protrusion.Methods A total of 541 patients with lumbar disc protrusion were included in this study.All the patients fulfilled the following criteria:the fibrous ring was broken,the protruded extent of nucleus pulposus was less than 10 mm and the dura sac and/or nerve root was compressed.The intradiscal injection of ozone combined with epidural injection of collagenase was performed in all patients.The patients were followed up through further consultation,letters,telephone or other ways.Five hundred and forty-one cases were followed up for 2-3 months(short-term),312 cases for 4-12 months(medium-term)and 115 cases for 13-18 months(long-term).The short-term,medium-term and long-term curative effects were evaluated with unified curative criteria,and the results were compared with that obtained with the treatment of epidural injection of collagenase only.Results The short-term,medium-term and long-term effective rate of selected cases was 95.9%(519/541),90.4%(489/541)and 87.2%(472/541),respectively.When combined application of two methods was performed,different degree of shrinkage of the protruded nucleus pulposus was obviously observed,with a mean shrinkage degree of 30.5%.The short-term,medium-term and long-term effective rate of simple collagenase chemonucleolysis was 89.5%,82.4%and 80.4%,respectively.Conclusion Intradiscal injection of ozone combined with epidural injection of collagenase is an effective treatment for lumbar disc protrusion when the fibrous ring is broken,the protruded extent of nucleus pulposus is less than 10 mm and the dura sac and/or nerve root is compressed.Its curative effect is superior to simple collagenase chemonucleolysis.Ozone is of clinical significance for producing the shrinkage of the nucleus pulposus.

Objective To investigate the curative effect and safety of percutaneous intradiscal injection of ozone combined with epidural injection of collagenase for the treatment of prominent lumbar disc protrusion.Methods A total of 541 patients with lumbar disc protrusion were included in this study.All the patients fulfilled the following criteria:the fibrous ring was broken,the protruded extent of nucleus pulposus was less than 10 mm and the dura sac and/or nerve root was compressed.The intradiscal injection of ozone combined with epidural injection of collagenase was performed in all patients.The patients were followed up through further consultation,letters,telephone or other ways.Five hundred and forty-one cases were followed up for 2-3 months(short-term),312 cases for 4-12 months(medium-term)and 115 cases for 13-18 months(ling-term).The short-term,medium-term and long-term curative effects were evaluated with unified curative criteria,and the results were compared with that obtained with the treatment of epidural injection of collagenase only. Results The short-term, medium-term and long-term effective rate of selected cases was 95.9%(519/541),90.4%(489/541)and 87.2%(472/541),respectively.When combined application of two methods was performed,different degree of shrinkage of the protruded nucleus pulposus was obviously observed,with a mean shrinkage degree of 30.5%.The short-term,medium-term and long-term effective rate of simple collagenase chemonucleolysis was 89.5%,82.4%and 80.4%,respectively.Conclusion Intradiscal injection of ozone combined with epidural injection of collagenase is an effective treatment for lumbar disc protrusion when the fibrous ring is broken,the protruded extent of nucleus pulposus is less than 10 mm and the dura sac and/or nerve root is compressed. Its curative effect is superior to simple collagenase chemonucleolysis. Ozone is of clinical significance for producing the shrinkage of the nucleus pulposus.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.