Epigenetic changes are important etiological factors of human tumor. The integrity of the genome is frequently challenged by the damage of DNA. However, the highly condensed structure of chromatin imposes significant obstacles on the repair processes. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by chromatin. Covalent histone modifications and ATP-dependent chromatin remodeling play important roles in the process of DNA repair. Recent advances of the epigenetic regulations in the repair process were summarized. New findings in the cellular responses to DNA double strand breaks and how histone modifications and chromatin remodeling contributes to DNA double strand break repair were introduced. Future challenges in this field are also discussed.

Objective To investigate the clinical efficacy and prognostic factors of radical hepatectomy of hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 760 HCC patients who were admitted to the First Affiliated Hospital of Nanjing Medical University from August 2003 to June 2015 were collected.Surgical procedures were determined according to the location,number and size of tumors and anatomical relations among vessels.Observation indicators included:(1)intra-and post-operative situations:surgical procedures,operation time,volume of intraoperative blood loss,cases of intraoperative blood transfusion,postoperative complications,duration of postoperative hospital stay and pathological examination;(2) follow-up:1-,3-,5-year overall and tumor-free survival situations;(3) prognostic factors analysis of HCC patients.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to January 2016.Measurement data with normal distribution were represented as-x±s.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method.The univariate analysis and multivariate analysis were done using the COX regression model.Results (1) Intra-and post-operative situations:all the 760 patients underwent successful operations,including 419 undergoing anatomical hepatectomy and 341 undergoing non-anatomical hepatectomy.R0 and R1 resections were respectively applied to 742 and 18 patients.Two patients were combined with portal vein resection and reconstruction and 1 was combined with resection and reconstruction of inferior vena cava.Operation time,volume of intraoperative blood loss and cases of intraoperative blood transfusion were (226± 115) minutes,(714±706) mL and 88,respectively.Fifty-five patients had postoperative complications,including 20 with abdominal effusion or abscess,16 with pleural effusion,9 with recurrent fever,8 with incisional infection,7 with intra-abdominal hemorrhage,6 with liver failure,3 with pyloric or intestinal obstruction and 2 with renal failure (some patients with multiple complications).Of the 55 patients with postoperative complications,7 with hemorrhage underwent reoperation or interventional therapy and other patients underwent conventional symptomatic treatment.Of 55 patients,5 patients died and other 50 patients were improved.Duration of postoperative hospital stay was (14±6) days.There were 457 patients with minimum margin of tumors ≤ 1.0 cm and 303 with minimum margin of tumors ＞ 1.0 cm.(2) Followup:all the 760 patients were followed up for 1-139 months,with a median time of 25 months.The overall and tumor-free median survival times were 59 months and 31 months,respectively.The 1-,3-,5-year overall and tumor-free survival rates were 81.7％,63.4％,47.9％ and 68.7％,44.9％,29.6％,respectively.(3) Prognostic factors analysis of HCC patients:results of univariate analysis showed that clinical symptoms,alpha-fetoprotein (AFP),Barcelona clinic liver cancer staging,surgical procedures,intraoperative blood transfusion,minimum margin of tumors,number and diameter of tumors,tumor capsule,tumor differentiation,vascular cancer embolus,macrovascular invasion and tumor staging of American Joint Committee on Cancer (AJCC) were related factors affecting prognosis of HCC patients after radical hepatectomy [HR =1.39,1.50,1.92,0.65,1.45,1.68,1.96,1.66,2.26,1.50,2.68,3.37,2.00,95％ confidence interval (CI):1.08-1.79,1.16-1.94,1.68-2.20,0.50-0.84,1.04-2.02,1.28-2.20,1.54-2.49,1.42-1.94,1.69-3.02,1.22-1.85,1.99-3.60,2.61-4.36,1.77-2.27,P＜0.05].Results of multivariate analysis showed that AFP,number and diameter of tumors,tumor differentiation and tumor staging of AJCC were independent factors affecting prognosis of HCC patients after radical hepatectomy (HR=1.61,1.62,1.31,1.40,1.78,95％CI:1.14-2.26,1.22-2.14,1.06-1.63,1.10-1.79,1.27-2.51,P ＜ 0.05).Conclusions The anatomical and non-anatomical hepatectomies are safe and feasible for optional HCC patients,with a good long-term outcome.AFP,number and diameter of tumors,tumor differentiation and tumor staging of AJCC are independent factors affecting prognosis of HCC patients after radical hepatectomy.

RecQ5 in mammalian cells has been suggested to suppress inappropriate homologous recombination. However, the specific pathway(s) in which it is involved and the underlining mechanism(s) remain poorly understood. We took advantage of genetic tools in Drosophila to investigate how Drosophila RecQ5 (dRecQ5) functions in vivo in homologous recombination-mediated double strand break (DSB) repair. We generated null alleles of dRecQ5 using the targeted recombination technique. The mutant animals are homozygous viable, but with growth retardation during development. The mutants are sensitive to both exogenous DSB-inducing treatment, such as gamma-irradiation, and endogenously induced double strand breaks (DSBs) by I-Sce I endonuclease. In the absence of dRecQ5, single strand annealing (SSA)-mediated DSB repair is compromised with compensatory increases in either inter-homologous gene conversion, or non-homologous end joining (NHEJ) when inter-chromosomal homologous sequence is unavailable. Loss of function of dRecQ5 also leads to genome instability in loss of heterozygosity (LOH) assays. Together, our data demonstrate that dRecQ5 functions in SSA-mediated DSB repair to achieve its full efficiency and in suppression of LOH in Drosophila.
Animals ; DNA Repair ; genetics ; DNA, Single-Stranded ; genetics ; Drosophila Proteins ; genetics ; metabolism ; Drosophila melanogaster ; genetics ; metabolism ; Loss of Heterozygosity ; genetics ; RecQ Helicases ; genetics ; metabolism

Objective    To explore the early results of Ozaki operation in children with aortic regurgitation. Methods    We retrospectively analyzed the clinical data of 15 patients with aortic regurgitation who received the Ozaki operation in our hospital from April 2017 to July 2019. There were 11 males and 4 females with an average operation age of 10.7±3.7 years. Besides preoperative evaluation, aortic regurgitation and cardiac function were evaluated on 1 day, 1 week, 1 month, 3 months, and 6-12 months after surgery. Results    In 14 (93.3%) patients , the aortic valve leaflets functioned well on 1 day, 1 month, 3 months, and 6-12 months, and the regurgitation grade was Ⅰ-Ⅱ, which was improved than before (P=0.001). The cardiac function of children recovered quickly after operation. There was no statistical difference in ejection fraction on 1 day, 1 month, 3 months, and 6-12 months after operation (P>0.05). No children died, and no other clinical event was found. Conclusion    The Ozaki technique of reconstructing a tricuspid aortic valve leaflet for the treatment of severe aortic regurgitation in children is effective in short term, and the persistence of its valve function remains to be determined in the long-term follow-up.

Objective    To explore the experience of surgical repair for congenital aortic stenosis (AS) in our center. Methods    We retrospectively reviewed the clinical data of 145 children diagnosed with AS, who underwent aortic repair from 2008 to 2019, with or without aortic insufficiency (AI), including 104 males and 41 females with a median age of 2.9 (0.6, 7.8) years. The preoperative and intraoperative data, early and long-term valvular function, long-term survival rate and freedom from reoperation and aortic valve replacment (AVR) were analyzed. Results    There were 120 patients receiving commissurotomy, 15 valvuloplasty with extra pericardium patch, and 25 AVR. The mean follow-up time was 0.25-11.20 (4.2±2.8) years. Survival rate at 10 years was 92.3%. Freedom from reoperation and AVR was 63.2% and 60.4%respectively. Multivariate analysis revealed that using a patch during surgery (P=0.036) was an independent risk factor for reoperation. A history of preoperative balloon dilation (P=0.029) and significant preoperative AI (P=0.001) contributed to AVR. Conclusion    Surgical treatment of congenital aortic valve stenosis in children is a safe and effective method that provides enough time to achieve a more definitive solution. Using a patch during surgery increases reoperation hazard. A history of previous balloon dilation and significant preoperative AI may result in AVR during the follow-up.

Objective To explore growth pattern of neo-aortic root as well as development of neo-aortic regurgitation after arterial switch operation (ASO) for Taussig-Bing anomaly. Methods From 2002 to 2017, the patients who received ASO, and were discharged alive from Shanghai Children’s Medical Center and followed up for more than 3 years were retrospectively involved in this study. Results A total of 127 patients were enrolled. There were 98 (77.2%) males, the median age at ASO was 73.0 d and the average weight was 4.7 kg. Forty-five (35.4%) children were complicated with mild or mild-to-moderate pulmonary insufficiency (PI) before ASO. The average follow-up time was 7.0 years. During the follow-up, 14 (11.0%) children presented moderate or greater neo-aortic regurgitation (neo-AR). The diameter of neo-aortic annulus and sinus of Valsalva was beyond normal range during the entire follow-up. The average diameter of neo-aortic annulus was 18.0 mm at 5 years and 20.5 mm at 10 years. The average diameter of sinus of Valsalva was 25.9 mm at 5 years and 31.1 mm at 10 years. Neo-AR continued to develop over time. The diameter of children who developed moderate or greater neo-AR was constantly larger than that of children who did not (χ2=18.3, P<0.001). Preoperative mild or mild-to-moderate PI was an independent risk factor for the development of moderate or greater neo-AR during mid-to-long term follow-up (c-HR=3.46, P=0.03). Conclusion The diameters of neo-aortic annulus and sinus of Valsalva of Taussig-Bing children who receive ASO repair continue to expand without normalization. The dilation of annulus correlates with the development of neo-AR. PI before ASO repair increases the risk of neo-AR development.

Objective    To explore the effect of LeCompte maneuver on in-hospital mortality and mid-to-long term reintervention after single-stage arterial switch operation in children with side-by-side Taussig-Bing anomaly. Methods     Clinical data of patients diagnosed with side-by-side Taussig-Bing anomaly and undergoing single-stage arterial switch operation in Shanghai Children’s Medical Center from 2006 to 2017 were retrospectively analyzed. Patients were divided into two groups based on whether LeCompte maneuver was performed: a LeCompte maneuver group and a non LeCompte maneuver group. The clinical data of two groups were compared. Results    Finally 92 patients were collected. LeCompte maneuver was performed in 32 out of 92 patients with a median age of 65.0 days and an average weight of 4.3 kg, among whom 24 (75.0%) were male. Fifteen (46.9%) patients received concomitant aortic arch repair while 12 (37.5%) patients were associated with coronary artery malformation. LeCompte maneuver was not performed in 60 patients with a median age of 81.0 days and an average weight of 4.8 kg, among whom 45 (75.0%) were male. Twenty-two (36.7%) patients received concomitant aortic arch repair while 35 (58.3%) patients were associated with coronary artery malformation. The average cardiopulmonary bypass duration of the LeCompte maneuver group showed no statistical difference from the non LeCompte maneuver group (179.0±60.0 min vs. 203.0±74.0 min, P=0.093). The in-hospital mortality of the two groups were 6 (18.8%) and 7 (11.7%), respectively, which also showed no statistical difference (P=0.364). The median follow-up period was 4.1 (1.6, 7.5) years for 79 patients with 8 lost to follow-up, and no death was observed. Kaplan-Meier curve and log-rank test showed no statistical difference in overall mid-to-long term reintervention rate (P=0.850) as well as right ventricular outflow tract and pulmonary artery reintervention rate (P=0.240) with or without LeCompte maneuver. Conclusion    Whether or not to perform LeCompte maneuver shows no statistical impact on in-hospital mortality and mid-to-long term reintervention rate of single-stage arterial switch operation for side-by-side Taussig-Bing anomaly.

ObjectiveTo observe the recovery of proprioception of the affected ankle over time after lateral ankle sprain accepting routine rehabilitation. MethodsFrom June, 2020 to June, 2022, 18 patients with lateral ankle sprain in Kunshan Rehabilitation Hospital underwent routine rehabilitation for twelve weeks. They were measured active and passive position sense of bilateral ankles using an isokinetic dynamometer before treatment, and four, eight and twelve weeks after treatment, respectively. ResultsThe active presentation difference of affected ankle reduced after treatment (F = 22.533, P < 0.001), but it was more than that of the healthy ankle at the same time (t > 4.419, P < 0.001). No significant improvement was found in passive presentation difference of affected ankle after treatment (F = 1.175, P > 0.05), and it was not significantly different from those of the healthy ankle at the same time (|t| < 0.646, P > 0.05). ConclusionProprioception of affected ankle has been impaired after lateral ankle sprain, and it can be recovered after rehabilitation, but cannot achieve the healthy level even after three months of training. Passive position sense as an index of proprioception needs more researches.

Objective    To discuss outcomes of arch reintervention for post-repair recoarctation in children. Methods    From 2009 to 2019, 48 patients underwent reintervention for post-repair recoarctation in Shanghai Children’s Medical Center. Of the 48 patients, 22 patients had surgical repair, 25 patients had balloon angioplasty (BA), and 1 patient had a stent implantation. The clinical data were analyzed, and the difference in time-to-event distribution between the surgical group and the BA group was determined by a log-rank test. Results    The median age at reintervention was 15.0 months (range, 3.0 months-15.1 years). The median weight at reintervention was 9.8 kg (range, 3.0-58.0 kg). The time to reintervention after initial repair was 12.5 months (range, 2.0 months-7.8 years). One patient (2.1%) died in hospital and 1 patient (2.1%) experienced arrhythmia after surgical repair. One late mortality (2.1%) occurred after surgical reintervention. One patient (2.1%) experienced aortic dissection after BA. No patient died after BA. Freedom from residual coarctation or new recurrences was 66.7%, 61.3%, and 56.9%, respectively, at 1, 2, and 5 years after reintervention. Freedom from residual coarctation or new recurrences was 90.0%, 81.8%, and 70.1%, respectively, at 1, 2, and 5 years after surgical repair. Freedom from residual coarctation or new recurrences was 52.0%, 48.0%, and 48.0%, respectively, at 1, 2, and 5 years after BA. Compared with BA, surgery-based reintervention had a lower incidence of residual coarctation or recurrences (χ2=4.400, P=0.036). Conclusion    Reintervention for recoarctation has favorable early outcomes. Compared with balloon angioplasty, surgical repair has a more lasting effect in relieving the recoarctation.

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.