1.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.
2.Clinical Efficacy of Perianal Surgery Combined With Anti-tumor Necrosis Factor-α Agents in Treating Perianal Fistulizing Crohn's Disease:A Meta-analysis
Zepeng CHEN ; Xingchen WANG ; Yibin PAN ; Yongqing CAO
Chinese Journal of Gastroenterology 2025;30(1):22-27
Background:The incidence of perianal fistulizing Crohn's disease is increasing and can seriously affect patients'quality of life.The efficacy of perianal surgery combined with biological agents for perianal fistulizing Crohn's disease remains to be clarified.Aims:To evaluate the clinical efficacy of perianal surgery combined with anti-tumor necrosis factor(TNF)-α agents in the treatment of perianal fistulizing Crohn's disease systematically.Methods:Cohort studies on perianal surgery combined with anti-TNF-α agents in the treatment of perianal fistulizing Crohn's disease were retrieved from PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang Data,and SinoMed.The retrieval time span was from the establishment of each database to October 30,2024.Literatures were enrolled according to the inclusion and exclusion criteria,and the data were extracted.Newcastle-Ottawa scale was used to evaluate the quality of literature.Meta-analysis was conducted by RevMan 5.4 software.Results:A total of 9 literatures involving 736 patients with perianal fistulizing Crohn's disease were enrolled.Meta-analysis showed that perianal surgery combined with anti-TNF-α agents shortened the healing time of anal fistula(WMD=-0.76,95%CI:-1.06--0.46;Z=4.91,P<0.000 01),decreased the recurrence rate of perianal fistula(OR=0.47,95%CI:0.26-0.84;Z=2.55,P=0.01),and reduced the perianal disease activity index(PDAI)score(WMD=-1.51,95%CI:-1.84--1.18;Z=8.91,P<0.000 01)when compared with perianal surgery alone.However,no significant differences in complete healing rate,partial healing rate,and reoperation rate were found between the two groups(all P>0.05).Conclusions:Perianal surgery combined with anti-TNF-α agents in the treatment of perianal fistulizing Crohn's disease demonstrates superior efficacy compared to perianal surgery alone in terms of shortening healing time,reducing recurrence rate and decreasing PDAI score.
3.Efficacy of laparoscopic versus open hepatectomy for intrahepatic bile duct stones based on propensity score matching
Baochen ZHAO ; Shunpei BAO ; Lilong QIAN ; Haoran SUN ; Zepeng CAO ; Bin ZHANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(8):1203-1209
Objective:To investigate the efficacy of laparoscopic versus open hepatectomy for intrahepatic bile duct stones based on propensity score matching. Methods:This study used a case-control design to retrospectively analyze 163 patients with intrahepatic bile duct stones who were treated at The Second Hospital of Anhui Medical University between February 2014 and February 2024. Based on the surgical approach, the patients were divided into two groups: the laparoscopic hepatectomy group ( n = 72) and the open hepatectomy group ( n = 91). Using 1:1 PSM, two groups with similar baseline clinical characteristics were created to compare perioperative outcomes, stone residual rates, and recurrence rates. Results:After PSM, a total of 52 matched pairs were successfully obtained. Compared with the laparoscopic hepatectomy group, the open hepatectomy group demonstrated a significantly shorter operative time [233.00 (180.00, 315.00) minutes vs. 313.00 (222.25, 405.75) minutes, Z = 3.41, P = 0.01]. However, no statistically significant differences were observed between the open hepatectomy and laparoscopic hepatectomy groups in terms of pre- to postoperative hemoglobin change [(22.69 ± 14.27) g/L vs. (20.63 ± 14.36) g/L, t = 0.73, P = 0.465], postoperative bile leakage [5.77% (3/52) vs. 11.54% (6/52), χ2 = 1.10, P = 0.25], hypoalbuminemia [82.69% (43/52) vs. 84.62% (44/52), χ2 = 0.07, P = 0.791], pulmonary infection [28.85% (15/52) vs. 40.38% (21/52), χ2 = 1.53, P = 0.216], surgical site infection [5.77% (3/52) vs. 1.92% (1/52), χ2 = 1.04, P = 0.308], intra-abdominal infection [1.92% (1/52) vs. 5.77% (3/52), χ2 = 1.04, P = 0.308], postoperative drainage tube removal time [8.00 (6.00, 11.75) days vs. 8.00 (6.25, 10.00) days, t = 0.05, P = 0.958], postoperative hospital stay [8.00 (9.00, 15.00) days vs. 9.00 (7.00, 12.50) days, t = -1.22, P = 0.222], residual stone rate [11.54% (6/52) vs. 9.62% (5/52), χ2 = 0.10, P = 0.750], and stone recurrence rate [13.46% (7/52) vs. 3.85% (2/52), χ2 = 3.04, P = 0.081]. All differences were statistically significant (all P > 0.05). Conclusions:Laparoscopic hepatectomy and open hepatectomy have comparable efficacy in the treatment of intrahepatic bile duct stones.
4.Clinical Efficacy of Perianal Surgery Combined With Anti-tumor Necrosis Factor-α Agents in Treating Perianal Fistulizing Crohn's Disease:A Meta-analysis
Zepeng CHEN ; Xingchen WANG ; Yibin PAN ; Yongqing CAO
Chinese Journal of Gastroenterology 2025;30(1):22-27
Background:The incidence of perianal fistulizing Crohn's disease is increasing and can seriously affect patients'quality of life.The efficacy of perianal surgery combined with biological agents for perianal fistulizing Crohn's disease remains to be clarified.Aims:To evaluate the clinical efficacy of perianal surgery combined with anti-tumor necrosis factor(TNF)-α agents in the treatment of perianal fistulizing Crohn's disease systematically.Methods:Cohort studies on perianal surgery combined with anti-TNF-α agents in the treatment of perianal fistulizing Crohn's disease were retrieved from PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang Data,and SinoMed.The retrieval time span was from the establishment of each database to October 30,2024.Literatures were enrolled according to the inclusion and exclusion criteria,and the data were extracted.Newcastle-Ottawa scale was used to evaluate the quality of literature.Meta-analysis was conducted by RevMan 5.4 software.Results:A total of 9 literatures involving 736 patients with perianal fistulizing Crohn's disease were enrolled.Meta-analysis showed that perianal surgery combined with anti-TNF-α agents shortened the healing time of anal fistula(WMD=-0.76,95%CI:-1.06--0.46;Z=4.91,P<0.000 01),decreased the recurrence rate of perianal fistula(OR=0.47,95%CI:0.26-0.84;Z=2.55,P=0.01),and reduced the perianal disease activity index(PDAI)score(WMD=-1.51,95%CI:-1.84--1.18;Z=8.91,P<0.000 01)when compared with perianal surgery alone.However,no significant differences in complete healing rate,partial healing rate,and reoperation rate were found between the two groups(all P>0.05).Conclusions:Perianal surgery combined with anti-TNF-α agents in the treatment of perianal fistulizing Crohn's disease demonstrates superior efficacy compared to perianal surgery alone in terms of shortening healing time,reducing recurrence rate and decreasing PDAI score.
5.Efficacy of laparoscopic versus open hepatectomy for intrahepatic bile duct stones based on propensity score matching
Baochen ZHAO ; Shunpei BAO ; Lilong QIAN ; Haoran SUN ; Zepeng CAO ; Bin ZHANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(8):1203-1209
Objective:To investigate the efficacy of laparoscopic versus open hepatectomy for intrahepatic bile duct stones based on propensity score matching. Methods:This study used a case-control design to retrospectively analyze 163 patients with intrahepatic bile duct stones who were treated at The Second Hospital of Anhui Medical University between February 2014 and February 2024. Based on the surgical approach, the patients were divided into two groups: the laparoscopic hepatectomy group ( n = 72) and the open hepatectomy group ( n = 91). Using 1:1 PSM, two groups with similar baseline clinical characteristics were created to compare perioperative outcomes, stone residual rates, and recurrence rates. Results:After PSM, a total of 52 matched pairs were successfully obtained. Compared with the laparoscopic hepatectomy group, the open hepatectomy group demonstrated a significantly shorter operative time [233.00 (180.00, 315.00) minutes vs. 313.00 (222.25, 405.75) minutes, Z = 3.41, P = 0.01]. However, no statistically significant differences were observed between the open hepatectomy and laparoscopic hepatectomy groups in terms of pre- to postoperative hemoglobin change [(22.69 ± 14.27) g/L vs. (20.63 ± 14.36) g/L, t = 0.73, P = 0.465], postoperative bile leakage [5.77% (3/52) vs. 11.54% (6/52), χ2 = 1.10, P = 0.25], hypoalbuminemia [82.69% (43/52) vs. 84.62% (44/52), χ2 = 0.07, P = 0.791], pulmonary infection [28.85% (15/52) vs. 40.38% (21/52), χ2 = 1.53, P = 0.216], surgical site infection [5.77% (3/52) vs. 1.92% (1/52), χ2 = 1.04, P = 0.308], intra-abdominal infection [1.92% (1/52) vs. 5.77% (3/52), χ2 = 1.04, P = 0.308], postoperative drainage tube removal time [8.00 (6.00, 11.75) days vs. 8.00 (6.25, 10.00) days, t = 0.05, P = 0.958], postoperative hospital stay [8.00 (9.00, 15.00) days vs. 9.00 (7.00, 12.50) days, t = -1.22, P = 0.222], residual stone rate [11.54% (6/52) vs. 9.62% (5/52), χ2 = 0.10, P = 0.750], and stone recurrence rate [13.46% (7/52) vs. 3.85% (2/52), χ2 = 3.04, P = 0.081]. All differences were statistically significant (all P > 0.05). Conclusions:Laparoscopic hepatectomy and open hepatectomy have comparable efficacy in the treatment of intrahepatic bile duct stones.

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