The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45γ [corrected], revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45γ [corrected] identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that: (1) dimerization of Gadd45γ [corrected] is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.
Amino Acid Motifs ; Animals ; Apoptosis ; radiation effects ; CDC2 Protein Kinase ; Cell Cycle ; Cell Survival ; Crystallography, X-Ray ; Cyclin B ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinases ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; chemistry ; genetics ; metabolism ; Mice ; Mutagenesis, Site-Directed ; Mutation, Missense ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Quaternary ; Ultraviolet Rays

Objective: To explore the efficacy of closed negative pressure irrigation and suction device (Patent number: Z200780013509.8) in the treatment of high perianal abscess. Methods: From January 2015 to December 2016, ≥18-year-old patients with primary high perianal abscess who were treated at our department were prospectively enrolled. Exclusion criteria: (1) recurrent perianal abscess; (2) complicated with anal fistula formation; (3) preoperative, intraoperative or postoperative physical therapy, and curettage treatment, negative pressure irrigation; (4) Crohn′s disease-related perianal abscess; (5) with immunosuppressive status, such as transplant recipients; (6) co-existence of malignant tumors, such as leukemia; (7) with diabetes; (8) those who could not receive long-term follow-up and were not suitable to participate in this study. According to the random number table method, the patients were randomly divided into negative pressure irrigation and suction group and routine drainage group. All patients were clearly diagnosed and the location and size of the perianal abscess were marked before surgery. These two groups were treated as follows: (1) Negative pressure irrigation and suction group: the skin was incised at a diameter of 1-2 cm at the site where the abscess fluctuated most obviously. After the abscess was removed, a closed negative pressure irrigation and suction device was installed and the pressure of -200 to -100 mmHg (1 mmHg=0.133 kPa) was maintained to keep the abscess cavity collapsed. Generally, the irrigation was stopped 5 days later or when the drainage was clear. The closed vacuum suction was maintained for 2 additional days, before the wound was sutured. (2) Conventional drainage group: conventional incision and drainage was carried out. The skin was cut at a diameter of 8 to 10 cm at the site of abscess with most obvious fluctuation. After the abscess was removed, normal saline gauze was used for dressing. Dressing was changed regularly until the wound healed. The efficacy, operative time, intraoperative bleeding, incision length, frequency of dressing change, pain index (visual analogue score, VAS score), postoperative healing time, complications, recurrence rate of perianal abscess, anal fistula formation rate were observed. The t test and χ² test were used for comparison between the 2 groups. Results: There were both 40 patients in the negative pressure irrigation and suction group and the conventional drainage group. There were 28 males and 12 females in negative pressure irrigation and suction group with a mean age of (38.3±12.0) years and mean disease course of (6.6±2.1) days. The abscess in pelvic-rectal space accounted for 50.0% (20/40) and the mean diameter of abscess was (8.0±3.7) cm. There were 26 males and 14 females in the conventional drainage group with a mean age of (37.1±11.8) years and mean disease course of (6.4±2.5) days. The abscess in pelvic-rectal space accounted for 55.0% (22/40) and the diameter of abscess was (8.2±3.5) cm. The differences in baseline data between two groups were not statistically significant (all P>0.05). Both groups successfully completed the operation. There was no significant difference in operative time between two groups (P>0.05). As compared to conventional drainage group, intraoperative blood loss in negative pressure irrigation and suction group was less [(12.1±5.5) ml vs. (18.3±4.4) ml, t=5.606, P<0.001], incision length was shorter [(2.3±0.8) cm vs. (7.6±1.7) cm, t=17.741, P<0.001], postoperative VAS pain scores at 1-, 3-, 7-, and 14-day after operation were lower [3.7±1.4 vs. 7.6±1.8, t=10.816, P<0.001; 3.0±1.3 vs. 6.8±1.6, t=11.657, P<0.001; 2.7±0.9 vs. 5.1±1.1, t=10.679, P<0.001; 1.2±0.3 vs. 1.6±0.4, t=5.060, P=0.019], the dressing change within 7 days after operation was less (3.5±1.2 vs. 12.6±2.7, t=19.478, P<0.001), postoperative healing time was shorter [(10.4±3.0) d vs. (13.5±3.8) d, t=4.049, P<0.001] and postoperative complication rate was lower [17.5% (7/40) vs. 2.5% (1/40), χ²=5.000, P=0.025]. During follow-up of 12 to 36 (24±5) months, the recurrence rate of perianal abscess within 1 year after operation and anal fistula formation rate in negative pressure irrigation and suction group were lower than those in conventional drainage group [5.0% (2/40) vs. 20.0% (8/40), χ²=4.114, P=0.042 and 2.5% (1/40) vs. 17.5% (7/40), χ²=5.000, P=0.025, respectirely]. The one-time cure rate of negative pressure irrigation and suction group and conventional drainage group was 92.5% (37/40) and 62.5%(25/40), respectirely (χ²=10.323, P=0.001). Conclusions The application of the negative pressure irrigation and suction device in the treatment of high perianal abscess can improve the efficiency of one-time cure, reduce postoperative pain, accelerate healing time, decrease the morbidity of postoperative complication and the rates of abscess recurrence and anal fistula formation, indicating an improvement of the treatment.

Objective To explore the efficacy of closed negative pressure irrigation and suction device (Patent number: Z200780013509.8) in the treatment of high perianal abscess. Methods From January 2015 to December 2016, ≥18?year?old patients with primary high perianal abscess who were treated at our department were prospectively enrolled. Exclusion criteria: (1) recurrent perianal abscess; (2) complicated with anal fistula formation; (3) preoperative, intraoperative or postoperative physical therapy, and curettage treatment, negative pressure irrigation; (4) Crohn′s disease?related perianal abscess; (5) with immunosuppressive status, such as transplant recipients; (6) co?existence of malignant tumors, such as leukemia; (7) with diabetes; (8) those who could not receive long?term follow?up and were not suitable to participate in this study. According to the random number table method, the patients were randomly divided into negative pressure irrigation and suction group and routine drainage group. All patients were clearly diagnosed and the location and size of the perianal abscess were marked before surgery. These two groups were treated as follows: (1) Negative pressure irrigation and suction group: the skin was incised at a diameter of 1?2 cm at the site where the abscess fluctuated most obviously. After the abscess was removed, a closed negative pressure irrigation and suction device was installed and the pressure of-200 to -100 mmHg (1 mmHg=0.133 kPa) was maintained to keep the abscess cavity collapsed. Generally, the irrigation was stopped 5 days later or when the drainage was clear. The closed vacuum suction was maintained for 2 additional days, before the wound was sutured. (2) Conventional drainage group: conventional incision and drainage was carried out. The skin was cut at a diameter of 8 to 10 cm at the site of abscess with most obvious fluctuation. After the abscess was removed, normal saline gauze was used for dressing. Dressing was changed regularly until the wound healed. The efficacy, operative time, intraoperative bleeding, incision length, frequency of dressing change, pain index (visual analogue score, VAS score), postoperative healing time, complications, recurrence rate of perianal abscess, anal fistula formation rate were observed. The t test and χ2 test were used for comparison between the 2 groups. Results There were both 40 patients in the negative pressure irrigation and suction group and the conventional drainage group. There were 28 males and 12 females in negative pressure irrigation and suction group with a mean age of (38.3±12.0) years and mean disease course of (6.6±2.1) days. The abscess in pelvic?rectal space accounted for 50.0% (20/40) and the mean diameter of abscess was (8.0±3.7) cm. There were 26 males and 14 females in the conventional drainage group with a mean age of (37.1±11.8) years and mean disease course of (6.4 ± 2.5) days. The abscess in pelvic?rectal space accounted for 55.0% (22/40) and the diameter of abscess was (8.2±3.5) cm. The differences in baseline data between two groups were not statistically significant (all P>0.05). Both groups successfully completed the operation. There was no significant difference in operative time between two groups (P>0.05). As compared to conventional drainage group, intraoperative blood loss in negative pressure irrigation and suction group was less [(12.1±5.5) ml vs. (18.3±4.4) ml, t=5.606, P<0.001], incision length was shorter [(2.3±0.8) cm vs. (7.6±1.7) cm, t=17.741, P<0.001], postoperative VAS pain scores at 1?, 3?, 7?, and 14?day after operation were lower [3.7±1.4 vs. 7.6±1.8, t=10.816, P<0.001; 3.0±1.3 vs. 6.8±1.6, t=11.657, P<0.001; 2.7±0.9 vs. 5.1±1.1, t=10.679, P<0.001; 1.2±0.3 vs. 1.6±0.4, t=5.060, P=0.019], the dressing change within 7 days after operation was less (3.5 ± 1.2 vs. 12.6 ± 2.7, t=19.478, P<0.001), postoperative healing time was shorter [(10.4±3.0) d vs. (13.5±3.8) d, t=4.049, P<0.001] and postoperative complication rate was lower [17.5% (7/40) vs. 2.5% (1/40), χ2=5.000, P=0.025]. During follow?up of 12 to 36 (24± 5) months, the recurrence rate of perianal abscess within 1 year after operation and anal fistula formation rate in negative pressure irrigation and suction group were lower than those in conventional drainage group [5.0% (2/40) vs. 20.0% (8/40), χ2=4.114, P=0.042 and 2.5% (1/40) vs. 17.5% (7/40), χ2=5.000, P=0.025, respectirely]. The one?time cure rate of negative pressure irrigation and suction group and conventional drainage group was 92.5% (37/40) and 62.5%(25/40), respectirely (χ2=10.323, P=0.001). Conclusions The application of the negative pressure irrigation and suction device in the treatment of high perianal abscess can improve the efficiency of one?time cure, reduce postoperative pain, accelerate healing time, decrease the morbidity of postoperative complication and the rates of abscess recurrence and anal fistula formation, indicating an improvement of the treatment.

Objective To explore the efficacy of closed negative pressure irrigation and suction device (Patent number: Z200780013509.8) in the treatment of high perianal abscess. Methods From January 2015 to December 2016, ≥18?year?old patients with primary high perianal abscess who were treated at our department were prospectively enrolled. Exclusion criteria: (1) recurrent perianal abscess; (2) complicated with anal fistula formation; (3) preoperative, intraoperative or postoperative physical therapy, and curettage treatment, negative pressure irrigation; (4) Crohn′s disease?related perianal abscess; (5) with immunosuppressive status, such as transplant recipients; (6) co?existence of malignant tumors, such as leukemia; (7) with diabetes; (8) those who could not receive long?term follow?up and were not suitable to participate in this study. According to the random number table method, the patients were randomly divided into negative pressure irrigation and suction group and routine drainage group. All patients were clearly diagnosed and the location and size of the perianal abscess were marked before surgery. These two groups were treated as follows: (1) Negative pressure irrigation and suction group: the skin was incised at a diameter of 1?2 cm at the site where the abscess fluctuated most obviously. After the abscess was removed, a closed negative pressure irrigation and suction device was installed and the pressure of-200 to -100 mmHg (1 mmHg=0.133 kPa) was maintained to keep the abscess cavity collapsed. Generally, the irrigation was stopped 5 days later or when the drainage was clear. The closed vacuum suction was maintained for 2 additional days, before the wound was sutured. (2) Conventional drainage group: conventional incision and drainage was carried out. The skin was cut at a diameter of 8 to 10 cm at the site of abscess with most obvious fluctuation. After the abscess was removed, normal saline gauze was used for dressing. Dressing was changed regularly until the wound healed. The efficacy, operative time, intraoperative bleeding, incision length, frequency of dressing change, pain index (visual analogue score, VAS score), postoperative healing time, complications, recurrence rate of perianal abscess, anal fistula formation rate were observed. The t test and χ2 test were used for comparison between the 2 groups. Results There were both 40 patients in the negative pressure irrigation and suction group and the conventional drainage group. There were 28 males and 12 females in negative pressure irrigation and suction group with a mean age of (38.3±12.0) years and mean disease course of (6.6±2.1) days. The abscess in pelvic?rectal space accounted for 50.0% (20/40) and the mean diameter of abscess was (8.0±3.7) cm. There were 26 males and 14 females in the conventional drainage group with a mean age of (37.1±11.8) years and mean disease course of (6.4 ± 2.5) days. The abscess in pelvic?rectal space accounted for 55.0% (22/40) and the diameter of abscess was (8.2±3.5) cm. The differences in baseline data between two groups were not statistically significant (all P>0.05). Both groups successfully completed the operation. There was no significant difference in operative time between two groups (P>0.05). As compared to conventional drainage group, intraoperative blood loss in negative pressure irrigation and suction group was less [(12.1±5.5) ml vs. (18.3±4.4) ml, t=5.606, P<0.001], incision length was shorter [(2.3±0.8) cm vs. (7.6±1.7) cm, t=17.741, P<0.001], postoperative VAS pain scores at 1?, 3?, 7?, and 14?day after operation were lower [3.7±1.4 vs. 7.6±1.8, t=10.816, P<0.001; 3.0±1.3 vs. 6.8±1.6, t=11.657, P<0.001; 2.7±0.9 vs. 5.1±1.1, t=10.679, P<0.001; 1.2±0.3 vs. 1.6±0.4, t=5.060, P=0.019], the dressing change within 7 days after operation was less (3.5 ± 1.2 vs. 12.6 ± 2.7, t=19.478, P<0.001), postoperative healing time was shorter [(10.4±3.0) d vs. (13.5±3.8) d, t=4.049, P<0.001] and postoperative complication rate was lower [17.5% (7/40) vs. 2.5% (1/40), χ2=5.000, P=0.025]. During follow?up of 12 to 36 (24± 5) months, the recurrence rate of perianal abscess within 1 year after operation and anal fistula formation rate in negative pressure irrigation and suction group were lower than those in conventional drainage group [5.0% (2/40) vs. 20.0% (8/40), χ2=4.114, P=0.042 and 2.5% (1/40) vs. 17.5% (7/40), χ2=5.000, P=0.025, respectirely]. The one?time cure rate of negative pressure irrigation and suction group and conventional drainage group was 92.5% (37/40) and 62.5%(25/40), respectirely (χ2=10.323, P=0.001). Conclusions The application of the negative pressure irrigation and suction device in the treatment of high perianal abscess can improve the efficiency of one?time cure, reduce postoperative pain, accelerate healing time, decrease the morbidity of postoperative complication and the rates of abscess recurrence and anal fistula formation, indicating an improvement of the treatment.