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: To investigate the relationships of intracranial compartment volumes with the severity of clinical symptoms before surgery, and the degree of symptom improvement one year after cerebrospinal fluid(CSF)shunt surgery in patients with idiopathic normal pressure hydrocephalus(iNPH). Methods: Twenty-one patients meeting the diagnosis criteria of international guidelines of iNPH and undergoing CSF shunt surgery in Department of Neurosurgery in our hospital from 2016 to 2017 were included.All patients underwent brain MRI measurement before surgery, and were evaluated by using 3-meter timed up and go test(TUG), minimum mental state examination(MMSE), idiopathic normal pressure hydrocephalus grading scale(iNPHGS)and modified Rankin scale(mRS)before and one year after CSF shunt procedures.The ventricular volume, brain volume, pericerebral CSF volume, total intracranial volume and Evans' index were measured in the pre-operative imaging of the brain.The following four pre-operative intracranial compartment volumes were calculated: the relative ventricular volume, brain volume ratio, pericerebral CSF volume ratio and the ratio of ventricular volume to pericerebral CSF volume. Results: The scores of gait, cognitive function and urinary function were improved after surgery in iNPH patients(all P<0.05). There were no significant difference in the correlation of intracranial compartment volumes(the relative ventricular volume, brain volume ratio, pericerebral CSF volume ratio and the ratio of ventricular volume to pericerebral CSF volume)and Evans' index with the severity of clinical symptoms including gait, cognitive function and urinary function before surgery, and with the degree of symptom improvement one year after surgery in iNPH patients(all P>0.05). There was no significant difference in intracranial compartment volumes between patients having improvement in mRS, TUG, MMSE and iNPHGS and patients having no improvement one year after surgery in iNPH patients(all P>0.05). Conclusions Patients with iNPH can benefit from CSF shunt surgery and have improvements of clinical symptoms including gait, cognitive function and urinary function.Preoperative intracranial compartment volumes(the relative ventricular volume, brain volume ratio, pericerebral CSF volume ratio and the ratio of ventricular volume to pericerebral CSF volume)and Evans' index have no correlations with the severity of clinical symptoms before surgery, and have no correlations with the degree of symptom improvement one year after surgery in iNPH patients.For this reason, preoperative intracranial compartment volumes and Evans' index cannot be used to predict whether or not CSF shunt surgery can improve specific clinical symptoms.

Objective:To evaluate the diagnostic efficiency and safety of endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)in lymph node staging of non-small cell lung cancer(NSCLC)in elderly patients.Methods:Thirty-five patients aged ≥70 years and 58 patients aged 60-69 years with NSCLC receiving EBUS-TBNA in our hospital from March 2015 to December 2018 were enrolled.All patients underwent EBUS for all visible mediastinal and hilar lymph nodes, and those with enlarged lymph nodes(short axis ≥6 mm)were further examined with TBNA.The diagnostic efficiency and safety of EBUS-TBNA were analyzed.Results:The sensitivity of EBUS-TBNA was 0.94, the specificity was 1.00, the Yoden index was 0.94, the positive predictive value was 1.00, and the negative predictive value was 0.82.Tumor staging was changed in 20 patients after EBU-TBNA, resulting in changes in assessment on tumor resectability in 5 cases.EBUS-TBNA had excellent agreement with postoperative pathology in evaluating resectability(Kappa=0.95). The sensitivity and specificity were 1.00 and 0.97, respectively.The incidence of complications of EBUS-TNBA was 6.5%.The elderly group had a worse performance status( P<0.05)compared with the control group, but the complication rates(5.7% vs 6.9%, P>0.05)were similar between the two groups. Conclusions:EBUS-TBNA is highly effective and safe in the diagnosis of NSCLC in patients aged 70 and older.

Objective:To explore the effects of pedicled rectus abdominis myocutaneous (PRAM)flap combined with free deep inferior epigastric artery perforator (DIEAP) flap carrying inguinal lymphatic flap in breast reconstruction and upper limb lymphedema treatment post radical mastectomy.Methods:From October 2014 to September 2016, 9 patients with upper limb lymphedema after mastectomy were treated with PRAM flap combined with free DIEAP flap carrying inguinal lymphatic flap for breast reconstruction and upper limb lymphedema treatment in Hunan Province Cancer Hospital. The patients were all females, aged 34-66 (44±7) years. The location of deep inferior epigastric artery perforator was detected by audible Doppler ultrasound blood stream detector and computed tomography angiography for designing combined tissue flap, with length of (25.32±0.27) cm, width of (13.14±0.76) cm, and thickness of (3.55±0.34) cm. The donor site of combined tissue flap was closed by suturing, and two or more tubes for negative pressure drainage were placed according to the situation of donor site and recipient site. Operation time and average placing time of negative pressure drainage tube, postoperative condition of combined tissue flap and the donor site, reconstructed breast condition, recovery of upper limb lymphedema were documented and followed up.Results:The operation time was 290-420 (396±55) min. The average retaining time of negative pressure drainage tube in breast was 5.9 d, while the average retaining time of negative pressure drainage tube in abdomen was 4.3 d. Ecchymoma occurred in DIEAP flap of one patient and in the flap donor site of another patient. Delayed healing was also seen in the rectus abdominis myocutaneous flap of a patient, which healed eventually after dressing change, and the other flaps survived well. The appearance of reconstructed breast was good with good elasticity, and no contracture or deformation occurred in the tissue flap. The upper limb lymphedema in 7 patients was alleviated in varying degrees, with 2.0-4.0 cm reduction in circumference. During follow-up of 12-24 months of 9 patients, averaged 17.5 months, with 6 patients received long term bandage pressure therapy and physical therapy to the affected limbs after operation and all patients were satisfied with appearances of the affected limbs. Neuropathic pain in affected limbs was significantly relieved in 2 patients and stopped aggravating in the other 2 patients. Only linear scar was seen in the donor site of abdomen without affecting obviously the function of abdomen.Conclusions:The PRAM flap combined with free DIEAP flap carrying inguinal lymphatic flap is an effective way for breast reconstruction and upper limb lymphedema treatment post mastectomy.

Objective:To explore the selection and effects of flap/myocutaneous flap repair methods for the defect after perineum tumor resection.Methods:From January 2011 to February 2017, 31 patients with vulvar tumor who were admitted to Hunan Cancer Hospital underwent repair of wound after tumor resection with various flaps/myocutaneous flaps. The patients were composed of 5 males and 26 females, aged 39-76 years, with 27 vulvar cancer and 4 Paget′s disease in primary diseases. The size of defects after vulvar tumor radical resection ranged from 8.0 cm×4.5 cm to 27.5 cm×24.0 cm. According to the theory of perforasome, the defects were repaired by the external pudendal artery perforator flap, deep inferior epigastric artery perforator flap, rectus abdominis myocutaneous flap, anterolateral thigh flap, internal pudendal artery perforator flap, gracilis myocutaneous flap, and profunda artery perforator flap based on the specific size and location of perineum and groin where the defect was located. According to the blood supply zone of flap, totally 17 local translocation flaps, 18 axial flaps/myocutaneous flaps, and 7 V-Y advancement flaps were resected, with an area of 7.0 cm×4.0 cm to 21.0 cm×13.0 cm. All the flaps/myocutaneous flaps were transferred in pedicled fashion, and the donor sites were closed without tension. The number of flaps/myocutaneous flaps, wound closure, flaps/myocutaneous flaps survival, and follow-up were observed and recorded.Results:Altogether 42 flaps/myocutaneous flaps were harvested in 31 patients. Two flaps/myocutaneous flaps were used in 11 cases for large circular defect repair. All the defects achieved tension-free primary closure. The blood supply of 32 flaps/myocutaneous flaps was good, while insufficient blood supply was noted in the other 10 flaps/myocutaneous flaps. Seventeen flaps/myocutaneous flaps survived smoothly. Wound dehiscence occurred in 5 flaps/myocutaneous flaps 8 to 14 days postoperatively, which was healed with dressing change. Temporary congestion was noted in 7 flaps/myocutaneous flaps 2 to 5 days postoperatively, which recovered without special treatment. Three flaps/myocutaneous flaps had infection 7 to 15 days postoperatively, two of which recovered after dressing change, while the other one had partial necrosis and received debridement and direct closure. Two flaps/myocutaneous flaps were totally necrotic 8 to 15 days postoperatively, which were repaired with pedicled rectus abdominis myocutaneous flap after debridement. Seven flaps/myocutaneous flaps had partial necrosis 7 to 20 days postoperatively and were healed after dressing change. Twenty-four patients were followed up for 9-38 months. The color of flaps/myocutaneous flaps was similar to that of the surrounding skin, the shape of vulva was natural, the movement of hip joint was not limited, the function of micturition and defecation was not affected, and tumor recurrence was noted in 3 patients.Conclusions:For the complicated large defect after perineum tumor resection, the flexible application of different forms of flaps/myocutaneous flaps to repair according to different areas regains the appearance and function. However, there are many complications, so it is necessary to further strengthen the postoperative care.

Objective:To investigate the relationship between satisfaction and quality of life of patients with breast reconstruction after mastectomy, and analyze the influencing factors of satisfaction.Methods:In this study, 157 female breast reconstruction patients who were treated in Hunan Cancer Hospital from January 2016 to June 2019 were selected as the object of this study. The BRECON-31 and QLQ-BR23 were used to assess satisfaction and quality of life respectively, and the clinical and demographic data were collected, Pearson correlation test was applied to analyze the correlation between satisfaction and quality of life, univariate analysis and multiple linear regression analysis were performed to investigate the influence factors of satisfaction.Results:A total of 157 patients, whose age was (41.8±8.3) years and median follow-up time was 11 months were included and 147 valid questionnaires were collected. The satisfaction score was 74.44±6.29, which meant patients with breast reconstruction after mastectomy had high satisfaction. There was a significant correlation between intimacy and body image ( r=-0.183, P=0.043), sexual function ( r=0.201, P=0.026), sexual interest ( r=0.204, P=0.029), breast symptoms ( r=-0.247, P=0.006) and arm symptoms ( r=-0.246, P=0.006) in patients with breast reconstruction after mastectomy, the patient’s self-awareness was significantly influenced by factors such as body shape ( r=-0.228, P=0.006), sexual function ( r=-0.293, P<0.001), sexual interest ( r=-0.258, P=0.003), breast symptoms ( r=-0.183, P=0.029), hair loss-induced annoyance ( r=-0.187, P=0.027). The result of univariate analysis showed that age ( P=0.047), tumor stage ( P=0.004), reconstruction method ( P<0.001), chemoradiotherapy ( P=0.043) were the influencing factors of total satisfaction score, multiple linear regression result showed that the reconstruction method ( P<0.001) was an independent influence factor of satisfaction score. The total satisfaction score of patients with autologous tissue reconstruction (75.99±5.94) was better than that of patients with autologous tissue combined prosthesis (71.08±4.99) and patients with simple prosthesis implantation (70.81±8.54). Conclusions:Mutual impact was identified for life quality and satisfaction among patients with breast reconstruction after mastectomy. In addition, age, tumor stage, reconstruction method and chemoradiotherapy are the influence factor of satisfaction. Among them, the reconstruction method is independent influence factor, and the breast reconstruction with autologous tissue is a better choice.

Objective:To investigate the relationship between satisfaction and quality of life of patients with breast reconstruction after mastectomy, and analyze the influencing factors of satisfaction.Methods:In this study, 157 female breast reconstruction patients who were treated in Hunan Cancer Hospital from January 2016 to June 2019 were selected as the object of this study. The BRECON-31 and QLQ-BR23 were used to assess satisfaction and quality of life respectively, and the clinical and demographic data were collected, Pearson correlation test was applied to analyze the correlation between satisfaction and quality of life, univariate analysis and multiple linear regression analysis were performed to investigate the influence factors of satisfaction.Results:A total of 157 patients, whose age was (41.8±8.3) years and median follow-up time was 11 months were included and 147 valid questionnaires were collected. The satisfaction score was 74.44±6.29, which meant patients with breast reconstruction after mastectomy had high satisfaction. There was a significant correlation between intimacy and body image ( r=-0.183, P=0.043), sexual function ( r=0.201, P=0.026), sexual interest ( r=0.204, P=0.029), breast symptoms ( r=-0.247, P=0.006) and arm symptoms ( r=-0.246, P=0.006) in patients with breast reconstruction after mastectomy, the patient’s self-awareness was significantly influenced by factors such as body shape ( r=-0.228, P=0.006), sexual function ( r=-0.293, P<0.001), sexual interest ( r=-0.258, P=0.003), breast symptoms ( r=-0.183, P=0.029), hair loss-induced annoyance ( r=-0.187, P=0.027). The result of univariate analysis showed that age ( P=0.047), tumor stage ( P=0.004), reconstruction method ( P<0.001), chemoradiotherapy ( P=0.043) were the influencing factors of total satisfaction score, multiple linear regression result showed that the reconstruction method ( P<0.001) was an independent influence factor of satisfaction score. The total satisfaction score of patients with autologous tissue reconstruction (75.99±5.94) was better than that of patients with autologous tissue combined prosthesis (71.08±4.99) and patients with simple prosthesis implantation (70.81±8.54). Conclusions:Mutual impact was identified for life quality and satisfaction among patients with breast reconstruction after mastectomy. In addition, age, tumor stage, reconstruction method and chemoradiotherapy are the influence factor of satisfaction. Among them, the reconstruction method is independent influence factor, and the breast reconstruction with autologous tissue is a better choice.

Solid papillary carcinoma of the breast is a rare breast papillary lesion that accounts for less than 1％ of breast cancers.The tumor is most common in elderly patients with imaging abnormalities or painless breast masses,histopathological manifestations of solid structure,frequent with mucous and/or neuroendocrine characteristics.The choice of surgical methods is mastectomy and simple mastectomy.At present,it is not well understood by clinicians and pathologists.In this paper,the clinicopathological features,treatment and prognosis of solid papillary carcinoma of the breast diagnosed by pathology in our hospital were retrospectively analyzed in order to improve the further understanding of this disease.

Objective: To explore the basic conditions and postoperative quality of life in patients undergoing oral vestibular thyroid surgery. Methods: A total of 128 patients undergoing oral vestibular thyroid surgery were enrolled in the Department of Head and Neck Surgery from March 2015 to April 2018. On the basis of routine thyroid tumor care, we used telephone, WeChat public platform, WeChat group, QQ, and Email. Questionnaires such as information technology and clinic review. Correlation analysis was performed using SPSS 22.0. Results: According to the analysis of SPSS statistical software, the postoperative recovery of the patients is good, and more than 95% of the patients have the feeling of "no" or "a little" for symptoms, and 91.8% (102/111) and 93.6% (104/111) of the patients have the perception of the general health status and life quality of the patients in the past 1 week respectively. Analysis of variance of postoperative life quality of patients, postoperative regression post was significantly correlated with postoperative social cognition, insomnia and economic difficulties of patients. The education level, occupation, marital status and family income of the patients all had significant influences on the postoperative economic status of the patients, and the differences were statistically significant (t=2.66-4.74, P<0.05). In the regression analysis of patients′ life quality, emotional function and physical function were independent risk factors affecting patients′ life quality, with statistical significance (t=-2.072, -5.564, P < 0.05). Conclusion Endoscopic thyroidectomy via oral vestibule has the advantages of good effect, beautiful appearance and high quality of life, which is worth popularizing and applying.

Objective: To explore the clinical application of the transverse upper gracilis flap (TUG) in breast reconstruction for breast cancer patients. Methods: From March 2010 to September 2016, 15 breast cancer patients received radical or modified radical mastectomy in Hunan Cancer Hospital, 8 cases of breast cancer were in stage Ⅰ and 7 cases was in stage Ⅱ. The age of patients ranged from 37 to 62 years old, (39.5±4.7) years. The TUG flap was used to reconstruct breast at the same time.The donor leg is placed in frog-leg position. Free TUG flap was harvested with gracilis muscular branch of profunda artery as pedicle. To keep tight connection between skin paddle and gracilis muscle, the perforators are not visualized. The flap was transferred to reconstruct breast, and the donor site was directly closed. Results: Mean operative time of unilateral reconstruction was 5 hours and (35± 44) minutes (with the range from 4 hours and 17 minutes to 6 hours and 5 minutes). Mean ischemia time was (52± 9 )minutes (with the range from 40 minutes to 1 hour and 16 minutes). The length of flap was (27.1±0.1) cm. The width of flap was (7.8±0.5) cm. The thickness of flap was (3.4±0.2) cm. The length of pedicle was( 6.8±0.5) cm.The average weight of flap was 350 g (ranged from 285 g to 525 g). All TUG flaps were survived. The shape, texture and elasticity of all reconstructed breasts were satisfactory, and there is no flap contracture deformation happened. Only linear scar left in the donor sites, without sacrifice of the function of thighs. All 15 patients were followed for 9-36 months (16.5 months on average). No local recurrence happened. Conclusion TUG flap can be safely harvested. It is reliable, with good texture. It is an alternative method for breast reconstruction after radical or modified radical mastectomy.