Background and purpose:Metabolic reprogramming occurs during tumor progression,and 1-acylglycerol-3-phosphate O-acyltransferase(AGPAT),as a key enzyme in the de novo synthesis of triacylglycerol(TAG),is closely associated with tumor progression.However,one of the isoforms,AGPAT5,has been studied in cancer in a very limited way,and this study aimed to provide a new perspective on the role of AGPAT5 in hepatocellular carcinoma and its potential molecular mechanisms,providing novel ideas for the diagnosis and treatment strategies of liver cancer.Methods:AGPAT5 was knocked down in a variety of hepatocellular carcinoma cell lines using lentiviral infection,and the effects of AGPAT5 on the functions of hepatocellular carcinoma cell proliferation,migration and resistance to anoikis were detected in vitro by experiments such as Taipan blue counting,scratching,transwell and plate cloning.The wild-type or enzyme activity-deficient form of AGPAT5 was rescued to investigate whether AGPAT5,as a metabolic enzyme,plays a classical role in regulating the migration of hepatocellular carcinoma cells.We constructed a tail vein metastasis model in nude mice to validate the cellular phenotype in vitro from the in vivo level.Immunoprecipitation mass spectrum(IP-MS)identified proteins interacting with AGPAT5 and verified by co-immunoprecipitation(coIP).Protein post-translational modification identification was performed to analyze the potential modification sites of AGPAT5,and in vitro experiments were performed to explore the effects of the point mutation before and after the point mutation on the migration of hepatocellular carcinoma cells.CoIP was performed to explore the binding of AGPAT5 to the interacting protein before and after the mutation of the site.We determined its role in cell phenotype by knocking down interacting proteins.Rescue experiments were used to verify whether AGPAT5 exerts its effects through the interacting protein.We detected the expression levels of AGPAT5 and the interacting protein in wild-type hepatocellular carcinoma cell lines to examine their correlation.Results:Knockdown of AGPAT5 increased the tolerance to serum-free starvation and promoted hepatocellular carcinoma cell migration,but did not affect proliferation and anoikis.However,deletion of enzyme activity did not affect the inhibition of hepatocellular carcinoma cell migration by AGPAT5.Knockdown of AGPAT5 promoted lung and liver metastasis of hepatocellular carcinoma cells in nude mice.AGPAT5 could interact with fibrillarin(FBL),and the interaction was strengthened under serum starvation conditions.Curbing FBL expression inhibited hepatocellular carcinoma cell migration,and the effect was similar to that of overexpression of AGPAT5.Inhibition of FBL expression weakened the promoting effect of AGPAT5 knockdown on hepatocellular carcinoma cell migration;In the hepatocellular carcinoma cell lines examined,AGPAT5 and FBL did not show any correlation at the protein level.The inhibitory effect of AGPAT5 on hepatocellular carcinoma cell migration was attenuated by the K201 site mutation,and the K201 site mutation attenuated the binding of AGPAT5 to FBL.Conclusion:Knockdown of AGPAT5 can significantly enhance the migratory ability of hepatocellular carcinoma cells.AGPAT5 can interact with FBL,and in the absence of serum starvation stimulation,AGPAT5 strengthen its binding to FBL through acetylation of the K201 site,thereby more effectively inhibiting FBL,consequently inhibiting the migration of hepatocellular carcinoma cells.But this inhibitory effect is not derived from the metabolic enzyme activity of AGPAT5,but driven by non-metabolic function.

Background With the increasing exposure to hazardous chemicals in the workplace and frequency of occupational injuries and occupational safety accidents, the acquisition of occupational exposure limits of hazardous chemicals is imminent. Objective To obtain more unknown immediately dangerous to life or health (IDLH) concentrations of hazardous chemicals in the workplace by exploring the application of quantitative structure-activity relationship (QSAR) prediction method to IDLH concentrations, and to provide a theoretical basis and technical support for the assessment and prevention of occupational injuries. Methods QSAR was used to correlate the IDLH values of 50 benzene and its derivatives with the molecular structures of target compounds. Firstly, affinity propagation algorithm was applied to cluster sample sets. Secondly, Dragon 2.1 software was used to calculate and pre-screen 537 molecular descriptors. Thirdly, the genetic algorithm was used to select six characteristic molecular descriptors as dependent variables and to construct a multiple linear regression model (MLR) and two nonlinear models using support vector machine (SVM) and artificial neural network (ANN) respectively. Finally, model performance was evaluated by internal and external validation and Williams diagram was drawn to determine the scopes of selected models. Results The ANN model results showed that \begin{document}$ {R}_{\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{i}\mathrm{n}}^{2} $\end{document}=0.8526 and \begin{document}$ {R}_{\mathrm{t}\mathrm{e}\mathrm{s}\mathrm{t}}^{2} $\end{document}=0.8505 respectively, root mean square (RMSE) error=0.5243, mean absolute error (MAE)=0.4610, internal and external validation coefficients \begin{document}$ {Q}_{\mathrm{l}00}^{2} $\end{document}=0.8476 and \begin{document}$ {Q}_{\mathrm{e}\mathrm{x}\mathrm{t}}^{2} $\end{document}=0.8905 respectively. By comparison, the performance verification parameters of the ANN model were superior to the MLR and SVM models, and all substances were in the applicable domain. Conclusion At present, the ANN model has the best performance in fitting ability, stability, and prediction, and is suitable for predicting IDLH concentrations of benzene and its derivatives. Predicting the IDLH concentraitons of benzene and its derivatives by QSAR method is an effective method, and provides a theoretical basis and technical support for the development of occupational health and safety.

Objective:To summarize and analyze the current application status of oral mucosal graft (OMG) technique in the repair of ureteral strictures in China, and clarify the feasibility, safety and effectiveness of this technique.Methods:The 175 patients who underwent repair of ureteral stricture using oral mucosal patches from June 2015 to February 2022 were etrospectively analyzed in 14 medical centers in China, including 49 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 32 cases in Affiliated Seventh Medical Center of PLA General Hospital, 3 cases in The Second Hospital of Anhui Medical University, 6 cases in The First Affiliated Hospital of Zhengzhou University, 56 cases in Peking University First Hospital, 3 cases in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 cases in Shanghai Sixth People' s Hospital, 4 cases in General Hospital of Estern Theater Command, 4 cases in Lanzhou University Second Hospital, 2 cases in Guizhou Province People 's Hospital, 2 cases in Peking University People' s Hospital, 5 cases in Jinzhou First People's Hospital, 5 cases in The First Affiliated Hospital of Wannan Medical College, 1 case in Shandong Provincial Hospital. In this study, 127 patients (72.6%) used lingual mucosal patches, 32(18.3%) labial mucosa, and 16(9.1%) buccal mucosa. The surgical approach for OMG ureteral reconstruction was mainly minimally invasive, with robot-assisted laparoscopy in 84 patients (48.0%), traditional laparoscopic surgery in 87 patients (49.7%), and open surgery in only 4 patients (2.3%). There were 133 males and 42 females with an average age of (35.0±17.2) years. The mean body mass index (BMI) and stenosis length were (23.1±4.1) kg/m 2 and (4.7±1.8) cm, respectively. The stricture was located in the left ureter in 116 patients, right ureter in 58 case and bilateral ureter in 1 case. The most common causes of ureteral stricture were endoscopic surgery in 88(50.3%)patients, congenital stricture in 55(31.4%)patients, failed ureteroplasty in 29(16.6%)patients, history of extracorporeal shock wave lithotripsy in 13(7.4%)patients, radiotherapy history in 3(1.7%)patients and other causes in 6(3.4%)patients. Strictures were mainly located in the upper ureter, accounting for 61.7% (108/175 cases), followed by 36.0% (63/175) at the ureteropelvic junction and 2.3%(4/175)in the middle ureter. According to the surgical methods, the patients were divided into robot-assisted laparoscopic surgery group ( n=84), traditional laparoscopic surgery group ( n=87)and open surgery group ( n=4). Subgroup analysis of patients in robot-assisted laparoscopic and traditional laparoscopic surgery groups was performed. There were no significant difference in preoperative data between the two groups except for age (32.0±18.3) years vs.(37.0±15.9)years, P=0.040], BMI[(22.5±4.3)kg/m 2 vs. (23.7±3.6)kg/m 2, P=0.028], and etiology of stenosis [endoscopic injury, 34(40.5%) vs. 53(60.9%), P=0.012]. Preoperative hydronephrosis and stricture length were assessed by CTU and ureterography. Ureterography 7-9 weeks after surgery showed patency of the reconstructed segment, or no recurrence of hydronephrosis was judged as success. Evaluate the operation method, operation time, success rate, length of OMG in repairing ureteral stricture between laparoscopic and robot-assisted groups. Results:The overall success rate of oral mucosal graft repair surgery reached 97.7%(171/175). The success rate of ureteral reconstruction in the two groups were 96.4%(81/84)and 98.9%(86/87), respectively ( P=0.351), and the difference was not statistically significant. There was no significant difference for operation time, intraoperative blood loss, and mean oral mucosal length between the robotic and laparoscopic groups[(244.7±85.8) min and (222.7±83.5)min ( P=0.116), (58.9±38.6) ml and (68.4±45.5) ml ( P=0.217), (5.0±2.0) cm and (4.6±1.5) cm ( P=0.350)], respectively.Postoperative complications were reported in 23 (13.1%) patients, such as fever, urinary leakage, lymphatic leakage, infection, but only 2 (1.4%) cases patients had complications of Clavien-Dindo score ≥ Ⅲ. The two patients developed urinary stricture after surgery with failed conservative treatment, and no urinary stricture occurred following endoscopic treatment.The short-term (three months after surgery)incidence of complications in the site where the oral mucosa was taken, such as difficulty in opening mouth, pain, and swelling, was 12.0% (21/175), and there was no significant difference for oral complications between patients harvesting different length of mucosal graft. Conclusions:Ureteroplasty with oral mucosal graft is a safe, feasible and reliable technique for ureteral reconstruction. At present, minimally invasive technology is the main surgical approach for ureteroplasty, and there is no significant difference in operation time and success rate between robotic surgery and laparoscopic surgery.

Objective To evaluate the clinical efficacy of ilioinguinal conjoined perforator flap transplantation pedicled with the superficial circumflex iliac artery,the anterior fourth lumbar artery or the posterior intercostal artery.Methods Between April,2005 to August,2015,6 patients diagnosed as large skin defects in the upper extremity were treated with ilioinguinal conjoined perforator flap transplantation pedicled with the superficial circumflex iliac artery,the anterior fourth lumbar artery or the posterior intercostal artery.The proximal flap blood supply was offered by the superficial circumflex iliac artery,and the distal flap blood supply was provided by the anterior fourth lumbar artery or the posterior intercostal artery.The maximal size of the flap was measured as 35.0 cm×15.0 cm,and the minimal size was 25.0 cm×9.0 cm.The donor sites of the flap were directly sutured.All cases were implemented by postoperative followup visit in hospital for observation of appearance,texture,functions and donor site of flaps.Results Postoperatively,all flaps survived.The follow-up time endured for 6 to 24 months.The flap thickness was appropriate with normal shape and soft texture.Protective sensation and perspiration function of the flap were restored.Linear scars alone were observed in the donor sites of the flap.Conclusion Ilioinguinal conjoined perforator flap transplantation pedicled with the superficial circumflex iliac artery,the anterior fourth lumbar artery or the posterior intercostal artery can extend the excision scope of the flap and provides sufficient blood supply for the flap.The flap texture is soft and can be directly sutured.This technique is an ideal option for repairing of large soft tissue defects of the upper extremity.

Objective To measure the tear film lipid layer thickness (LLT) in dry eye patients and investigate the correlations of LLT with ocular surface signs.Methods One hundred and thirty dry eye patients (130 eyes),including 64 meibomian gland dysfunction (MGD) patients and 66 non-MGD patients,were included in this study.LLT,break-up time (BUT),fluorescein staining (FL),Marx's line (ML) score and Schirmer I test were performed and examined.The distribution of LLT in different age groups and the correlations between LLT and other examinations were analyzed.Results There was significant difference in LLT among different age groups (P =0.007),while LLT was not significantly different between male and female in each age group (P ＞ 0.05).LLT was positively correlated with age (r =0.334,P ＜ 0.001) and was not correlated with sex (r =0.107,P =0.226).LLT was positively correlated with upper eyelid ML score (r =0.295,P =0.001) and lower eyelid ML score (r =0.233,P =0.008).There was no significant correlation of LLT with BUT,FL or Schirmer Ⅰ test (all P ＞0.05).In the MGD group,there were positive correlations of LLT with upper eyelid ML score and lower eyelid ML score (all r =0.306,P =0.014),and no correlation of LLT with other examinations (all P ＞ 0.05).In the non-MGD group,there was no correlation of LLT with other examinations (all P ＞ 0.05).In a multivariate linear regression analysis,age and upper eyelid ML score were significantly related to LLT (β =0.254,P =0.005 for age and β =0.207,P =0.022 for upper eyelid ML score) in all dry eye patients.Age was the only factor related to LLT (β =0.382,P =0.002) in the MGD group.Upper eyelid ML score and lower eyelid ML score were higher in the MGD group than the non-MGD subgroup (all P ＜ 0.001).Conclusion LLT is positively correlated with age and ML score in dry eye patients.The measurement of tear film LLT,as an auxiliary examination in the diagnosis of dry eye disease,should be analyzed with the influential factors including age.

Objective:To evaluate the clinical effect of retroperitoneoscopic renal pedicle lymphatic disconnection via extra-adipose capsule in the management of chyluria and to discuss the management of its complications.Methods:From August 2013 to June 2008,five patients with chyluria were admitted. All the patients were female,aged from 26 to 73 years,and disease course from 1 to 10 years.All the five patients had complained of intermittently voiding milky urine with varying degrees of weight loss,and fa-tigue,of whom two presented with flank pain and one with anemia.Their urine chyle tests were con-firmed to be positive.Preoperative cystoscopy found that chyluria was from the left side in 3 cases,and from the right side in 2 cases.Their proteinuria ranged from +to ++++.All the cases had been treated with the modified procedure by which lymphatic ligation was performed to hilar vessels and proximalureter via extra-adiposecapsule without disconnection of perirenal fat tissues.The operation time,intraoperative blood loss,postoperative intestinal function recovery,catheter time,drainage tube removal time and com-plications during operation were collected.Results:All the five cases were performed successfully.The operation time ranged from 75 to 170 minutes,mean (126.0 ±39.6)minutes,with the intraoperative blood loss 20 to 60 mL,mean (38.0 ±16.4)mL,and the postoperative intestinal function recovery time 1 to 3 days,mean (1.9 ±0.4)days.The catheter time was 1 to 4 days,mean (2.1 ±0.3)days and the drainage tube removal time ranged from 3 to 15 days,mean (9.3 ±1.8)days.Postoperatively lym-phorrhagia was found in two cases.No renal vessels injury occurred during operation.Chyluria of all the patients disappeared on the operation day with negative chyluria test after surgery.Furthermore,urine test revealed that proteinuria was totally negative.No recurrence was detected in our patients in the 9 to 31 months’follow-up.Conclusion:This modified procedure does not have to disconnect perirenal fat tissues and nephropexy during operation.It was characterized with shorter operation time,definitive effect and fewer complications.

Objective To explore the efficacy of transplantation of a U-shaped ilioinguinal flap in the re pair of skin and soft tissue defects of the extremity.An axial flap based on the superficial iliac circumflex artery and trimmed to a subdermal vascular network flap was used for the procedures.Methods Seven patients with skin and soft tissue defects treated between June,2009 and May,2014 were studied.The patients were 22-45 years of age (mean,32 years),and included 5 males and 2 females.Four patients had punch-press injuries,1 patient had a hot-crush injury,and the remaining 2 patients were injured in the accidents.The wound sizes were 14.0 cm × 10.0 cm to 6.0 cm × 5.0 cm,with a varying extent of exposed tendons and bones.Repairs were performed using free ilioinguinal flaps,which were 15.0 cm × 11.0 cm to 7.0 cm × 5.0 cm in size.The axial flap was trimmed to a U-shaped subdermal vascular network flap and transplanted to the recipient site with anastomosis of blood vessels.Results All transplanted flaps survived.Four patients were followed for 1-6 months,with a mean duration of follow-up of 4 months.The trimmed flaps showed gradual reddening immediately after surgery,and the capillaries were recovered with a flat surface.Re-examination 3 months after surgery showed that the flaps were thin and flexible and met the aesthetic demand.No obvious pigmentation occurred,and the donor site was sutured directly,leaving only linear scars.Conclusion Repair of skin and soft tissue defects of the extremity using a U-shaped trimmed ilioinguinal flap has the advantages of a hidden donor site,small scar,and conformity to aesthetic requirements.The trimmed flaps are preferred over untrimmed flaps in terms of color and texture.The former flap is thinner,meets the aesthetic demand,and achieves a better efficacy.

Objective:To compare various data of open pyeloplasty,laparoscopic pyeloplasty and en-dopyelotomy as a treatment of ureteropelvic junction obstruction(UPJO),and to investigate and discuss the feasibility and effect of the three methods.Methods:In the study,109 cases of UPJO treated by dif-ferent surgical approaches in Peking University People’s Hospital from January 2004 to December 2014 were retrospectively investigated.The patients were divided into three groups according to the treatment they received:open peyloplasty group (32 cases),laparoscopic peyloplasty group (31 cases)and en-dopyelotomy group (46 cases).We compared the data of the operative time,intraoperative blood loss, perioperative complications and post-operative hospital stay among the three groups.The mean follow-up time was(51.9 ±40.1 )months (6 -132 months).Results:None of the laparoscopic peyloplties was converted to open peyloplasty.All endpyelotomies were successfully completed.The operative time was as follows:laparoscopic peyloplasty group (195.97 ±55.22)min,open peyloplasty group (121.19 ± 33.95)min and endopyelotomy group (74.04 ±33.95 )min,and there were significant differences among the three groups respectively(P <0.001 ).There was no significant difference on the operative blood loss between open peyloplasty group and laparoscopic peyloplasty group (P =0.163).The opera-tive blood loss of endopyelotomy group was 5(0,310)mL,which was lower than the other two groups,and this result had significant differences with the other two groups respectively(P <0.001).There were sig-nificant differences on the post-operative hospital stay (days)among open peyloplasty group,laparoscopic peyloplasty group and endopeylotomy group (P <0.05,respectively).The success rate was comparable between open peyloplasty group and laparoscopic peyloplasty group(93.8% vs.90.3%,P =0.672), while the endopeylotomy group had a lower success rate compared with both open surgery group and laparo-scopic group(69.6% vs.93.8%,P =0.01;69.6% vs.90.3%,P =0.048,respectively).The complica-tion rates of open peyloplasty group,laparoscopic peyloplasty group and endopeylotomy group were compa-rable(15.6%,16.1% and 13.0%,respectively,P >0.05).Conclusion:The laparoscopic peyloplasty group had a longer operative time than open peyloplasty group,while its post-operative stay was shorter. There was no significant difference on the operative blood loss between open peyloplasty group and laparo-scopic peyloplasty group.Although the success rate of endopyelotomy was lower than those of the other two groups,it had advantages over the aspect of operative time,operative blood loss and post operative stay.

ObjectiveTo report our experience and assess the safety and efficacy of ultrasound-guided percutaneous nephrolithotomy (PCNL) with ultrasonic and pneumatic lithotripters for complete renal staghorn stones.MethodsFrom Jan 2006 to Jan 2015, 128 patients (142 kidneys) with complete staghorn stones underwent PCNL, included 14 patients with bilateral renal complete stones,13 patients with solitary or founctional solitary kidney, 22 patients with renal insufficiency, 25 patients with renal empyema, 4 patients with spine malformation, ultrasound-guided PCNL were performed. Stones were fragmented and cleared using a combination of ultrasonic and pneumatic lithotripters.ResultsAll PCNL procedures were successful. Successful access to the collecting system was 100%. Mean operation time was 64.5±39. 1min (range 30–150). The primary stone-free rate of PCNL was 76.8%(109/142). Most of the renal stones(63.4%, 90/142)were managed satisfactorily by a single tract,a second tract was used in 25 renal stones(17.6%, 25/142). There were 36 auxiliary procedures (24 second PCNL and 3 third PCNL and 9 extracorporeal shock wave lithotripsy). One month after treatment, the overall stone-free rate was 85.2%(121/142). Six patients (4.2%) received blood transfusion,three patients(2.1%) received angiography and embolization . Three patients (2.1%) with infective shock were cured by intravenous antibiotics and antishock treatments. Three patients with temporary renal function receded were observed in solitary kidney for two tracts PCNL. No other severe complications occurred. The mean postoperative stay was 5.2 days (range 2–12). Conclusion: Ultrasound-guided Percutaneous Nephrolithotomy with ultrasonic and pneumatic lithotripters for management of renal complete staghorn stones is safe, effective, and worthy of wider use in clinical practice.

Objective:To compare the efficacy and safety of tubeless percutaneous nephrolithotomy ( tubeless-PCNL) and ureteroscopic lithotripsy ( URL) in treatment of impacted upper-ureteral calculi ≥1.5 cm in size.Methods:Patients with ureteral stones sized ≥1.5 cm and lodged above the fourth lum-bar vertebra who were treated between September 2009 and July 2013 in Peking University People ’ s Hos-pital were retrospectively analyzed .In the study , 182 patients underwent tubeless-PCNL or URL treat-ment respectively , and the operation success rates were compared .The duration of operation , intraopera-tive blood loss ( average hemoglobin decrease ) , complications , mean hospital stay and residual stone rates were also compared.Results: Fifty-four patients underwent tubeless-PCNL treatment,the average stone size was (1.9 ±0.4) cm,nephrostomy tubes were placed in two patients ,and the operation success rate was 96.3%(52/54).In the rest of the 52 patients,and the mean operation time was (30.1 ±14.8) minutes with an average postoperative hemoglobin decrease of (10.2 ±6.1) g/L, and the mean hospital stay was (3.0 ±1.4) days.Only one of the patients had residual fragments (2%).The main complica-tions included minor perirenal hematoma in 1 patient, fever in 2 patients, elevated blood WBC in 11 patients,and analgesics requirement in 3 patients.In the study, 128 patients were treated with URL,the average stone size was (1.7 ±0.3) cm.19 procedures failed,and 10 patients were converted to PCNL, extracorporeal shock wave lithotripsy was executed subsequently after double -J stent placement in 5 patients,and migration of calculi or stone fragments happened in 4 patients.The mean operative time was (51.3 ±25.5) minutes for the remaining 109 patients with a hemoglobin reduction of (5.2 ±7.2) g/L. The mean hospital stay was (2.9 ±1.3) days, and residual stones were found in 13 of the 109 patients (11.9%).The main complications included fever in 3 patients, elevated blood WBC in 42 patients, an-algesics requirement in 13 patients because of pain in the urethra or flank .The size of the stones between the two group didn ’ t show significant difference ,but the success rate of the tubeless-PCNL procedure was significantly higher .Except that hemoglobin decrease was slightly higher in the tubeless-PCNL group ,the mean operative time , the rate of residual stones and rate of complications of the tubeless-PCNL group were lower significantly.Conclusion:Treating stones above 4th lumbar vertebra larger than 1.5 cm were challenging .It is difficult to treat these stones with URL because of a high probability to fail , but on the contrary, tubeless-PCNL was more likely to be performed successfully .For surgeons experienced with the PCNL technology, treating stones≥1.5 cm with tubeless-PCNL procedure may turn out to be more effi-cient and with a higher operation success rate , and the risk of complications was lower without lengthe-ning the postoperative hospital stay .