Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.Methods C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide(4NQO,50 mg/L).Lingual mucosa samples,being representative of normal tissue(week 0)and early(week 12)and advanced(week 28)tumorigen-esis,were harvested for microarray and methylated DNA immunoprecipitation sequencing(MeDIP-Seq).The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1(SMAD1)were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.Results The cytosine guanine island(CGI)methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks.The promoter methylation level at 12 weeks exceeded that at 0 weeks.Notably,208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0,12,and 28 weeks.The mRNA of SMAD1 was upregulated,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.

Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

Objective:To study the application of scenario simulation teaching combined with modular training in nursing education of medical rescue in manned space flight.Methods:Twenty nurses from the medical rescue team of Strategic Support Force Characteristic Medical Center were selected as the research objects. The research objects were randomly divided into the scenario simulation combined with practical training group (practical training group, n=10) and traditional teaching group (control group, n=10). Scenario simulation teaching combined with modular training and traditional teaching were used to carry out nursing training. After the training, theoretical assessment, operation assessment and satisfaction survey were organized. Results:The scenario simulation teaching combined with modular training group was significantly better than the traditional training group in theory assessment, operation assessment and satisfaction survey of nursing staff (all P<0.05). Conclusions:Scenario simulation teaching combined with modular training has obvious teaching effect, which can improve the ability and quality of nursing staff, and help to complete the manned space medical rescue mission efficiently.

Objective:To review the characteristics and coping strategies of the rescue and landing medical support mission of Shenzhou-14 manned spacecraft.Methods:The characteristics of rescue and landing medical support mission of Shenzhou-14 manned spacecraft was analyzed, and the coping strategies and experience were discussed.Results:(1) The characteristics of rescue and landing medical support mission of Shenzhou-14 manned spacecraft included: long time in space station and high-intensity space missions; high-density space medical support mission in short term; special environmental factors in severe cold night; complex terrain of landing site; and the young medical support team. (2) The main coping strategies of rescue and landing medical support mission of Shenzhou-14 manned spacecraft included: strengthened the organization and leadership and improved the training model; reinforcement learning the medical treatment plan and strengthened the medical rescue skills training; optimized the carrying equipment and added the heat preservation and lighting measures; improved the medical rescue process and perfected the emergency plan; emphasized on the scientific research as important as mission; and strengthened the physical exercise and cold resistance exercise.Conclusions:The characteristics and coping strategies of rescue and landing medical support mission of Shenzhou-14 manned spacecraft are summarized to provide the experience for space medical rescue and offer the support for China's manned space industry.

Objective:To compare perioperative differences between posterior lumbar interbody fusion(PLIF)by a posterior median approach or open transforaminal lumbar interbody fusion(TLIF)and minimally invasive surgery TLIF(MIS-TLIF)by a paravertebral approach for lumbar spondylolisthesis(Ⅰ~Ⅱ°)in elderly patients.Methods:A retrospective study was conducted to analyze clinical data of patients aged 60 years and over with lumbar spondylolisthesis(n=68)who underwent PLIF or MIS-TLIF from January 2014 to December 2017.Patients were divided into the PLIF group(n=40, 12 males and 28 females)and the MIS-TLIF group(n=28, 6 males and 22 females)according to the type of surgery.Differences in operating time, blood loss, exposure frequency, postoperative drainage volume, indwelling duration, hospital stay length and complications were compared between the groups.Results:There was no significant difference in operative time between the PLIF group and the MIS-TLIF group(156±51)min vs.(153±38)min( P=0.77). There were significant differences in intraoperative blood loss and radiation exposure frequency between the PLIF group and the MIS-TLIF group(458±272)ml vs.(157±104)ml( P<0.001); (6.7±1.5)times vs.(30.6±6.9)times( P<0.01). There was no significant difference in intraoperative complications between the PLIF group and the MIS-TLIF group(25% or 10/40 vs.7.1% or 2/28, P=0.057). There were more postoperative drainage, longer indwelling time and hospitalization in the PLIF group than in the MIS-TLIF group(664±351)ml vs.(210±127)ml( P<0.001); (3.7±2.9)d vs.(2.2±0.8)d( P=0.002); (9.2±3.6)d vs.(6.9±1.7)d( P=0.001). The incidence of postoperative neurological complications was not significantly different between the PLIF group and the MIS-TLIF group(7.5% or 3/40 vs.14.3% or 4/28, P=0.365). The incidence of postoperative non-neurological complications was higher in the PLIF group than in the MIS-TLIF group(27.5% or 11/40 vs.7.1% or 2/28, P=0.036). Conclusions:Compared with PLIF, MIS-TLIF has the advantages of less intraoperative bleeding and postoperative drainage, shorter indwelling duration of urinary catheters, shorter hospital stays and fewer complications of non-neurological complications in treating Ⅰ-Ⅱ degree lumbar spondylolisthesis in the elderly, but it requires more radiation exposure.

Objective To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors. Methods A case?control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non?complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications. Results Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non?surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6 ± 12.6) days vs. (14.2 ± 6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960?8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862?29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357?21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214?12.658, P<0.001) were the independent risk factors of postoperative complications. Conclusions Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.

Objective To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors. Methods A case?control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non?complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications. Results Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non?surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6 ± 12.6) days vs. (14.2 ± 6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960?8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862?29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357?21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214?12.658, P<0.001) were the independent risk factors of postoperative complications. Conclusions Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.

Bariatric surgery is an effective method for the treatment of obesity and type 2 diabetes mellitus. Morbidly obese patients usually have metabolic syndromes, as such, surgeons need to choose the reasonable surgical methods for patients according to their individuality and particularity. Hiatal hernia is a very common disease prevalent in obese patients and could induce gastroesophageal reflux, which increases the difficulty of bariatric surgery and proposes higher demands on choice of surgical methods to surgeons. It is important to recognize the presence of the hiatal hernia preoperatively and choose a more effective procedure of bariatric surgery to decrease the incidence of postoperative complications.

Objective: To investigate the efficacy and feasibility of laparoscopic resection for gastric gastrointestinal stromal tumor (GIST) in unfavorable location by comparing with open surgery. Methods: Clinicopathological and follow-up data of 176 patients with gastric GIST in unfavorable location admitted at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to December 2017 were analyzed retrospectively. There were 94 males and 82 females, aging of (57.4±12.7) years (range: 20-90 years). Of the 176 patients, 64 underwent laparoscopic surgery (laparoscopic group) and 112 underwent open surgery (open group). One-to-one propensity score matching (PSM) was performed to balance the covariance between laparoscopic group and open surgery group. Before PSM, the differences between the two group in tumor size and modified National Institutes of Health risk classification were significant. After PSM, there were 63 pairs (63 cases in laparoscopic group and 63 cases in open group) and the baseline characteristics were comparable between the two groups(P>0.05). The difference of short-term outcome between the two groups were compared using t test, χ² test or Wilcoxon rank-sum test. The survival curve was established by Kaplan-Meier method and the Log-rank test was used to compare the survival of the two groups. Results: The operation time of laparoscopic group was shorter ((141.6±100.6) minutes vs. (100.4±67.7) minutes, t=2.681, P=0.008), the hospitalization cost was higher ((5.2±0.7) ten thousand yuan vs. (4.2±0.8) ten thousand yuan, t=7.357, P=0.000) than open group. The time to first flatus ((49.1±8.2) hours vs. (71.0±4.6) hours, t=-18.482, P=0.000) and preoperative hospital stay ((10.3±6.0) days vs. (14.8±7.6) days, t=-3.717, P=0.000) was shorter in laparoscopic group. With a median follow-up time of 44 months (range: 10 to 154 months), the 1-, 3-, 5-year relapse-free survival rates in the laparoscopic group and open group were 98.3%, 92.1%, 92.1% and 100%, 86.3%, 83.2%, respectively (χ²=0.696, P=0.404). The 1-, 3-, 5-year overall survival rates in the laparoscopic group and open group were 96.6%, 94.7%, 94.7% and 100%, 91.1%, 81.4%, respectively (χ²=0.366, P=0.545). Conclusions In experienced medical centers, laparoscopic resection is safe and feasible for GIST in unfavorable location. Compared to open surgery, laparoscopic resection achieves a faster postoperative recovery and a similar long-term prognosis.