Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Objective To establish a cellular model of Parkinson disease by treating retinoic acid(RA)-differentiated SH-SY5Y cells with α-synuclein preformed fibrils(α-Syn PFF).Methods SH-SY5Y cells were divided into undifferentiated and RA-differentiated groups.The expression levels of tyrosine hydroxylase(TH),dopamine transporter(DAT),lymphocyte activation gene 3(LAG3),and Nestin proteins in the cells were detected using Western blotting,whereas those of microtubule-associated protein 2(MAP2)and neu-ronal nuclei(NeuN)were detected using immunofluorescence staining.Furthermore,RA-treated SH-SY5Y cells were divided into control and α-Syn PFF groups,and their levels of chromatin condensation were detected using Hoechst 33342 staining.Nitric oxide(NO)levels were measured using a NO assay kit.Additionally,the protein levels of TH,poly(ADP-ribose)(PAR),and poly(ADP-ribose)poly-merase(PARP)in these cells were detected using Western blotting,whereas their expression levels of phosphorylated α-Syn(pS129-α-Syn)and phosphorylated histone H2AX(γH2AX)were detected using immunofluorescence staining.Results Treatment with RA resulted in a reduction in cell body size and the elongation of protrusions in SH-SY5Y cells.The results of Western blotting showed that RA treatment could increase the TH,DAT,and LAG3 levels and decrease the Nestin level in SH-SY5Y cells(P＜0.05).α-Syn PFF treat-ment decreased the TH protein level and increased the PAR,PARP-l,and cleaved PARP-1 levels in differentiated SH-SY5Y cells(P＜0.05).According to the immunofluorescence results,RA treatment increased the expression levels of MAP2 and NeuN in SH-SY5Y cells(P＜0.001).The α-Syn PFF treatment increased the expression levels of γH2AX and pS129-α-Syn in RA-differentiated SH-SY5Y cells(P＜0.01).The Hoechst 33342 staining results showed that α-Syn PFF treatment led to chromatin condensation in the differentiated SH-SY5Y cells(P＜0.001)and increased the NO levels(P＜0.01).Conclusion A cellular model of Parkinson disease can be established by treating RA-differentiated SH-SY5Y cells with α-Syn PFF.

Objective To establish a cellular model of Parkinson disease by treating retinoic acid(RA)-differentiated SH-SY5Y cells with α-synuclein preformed fibrils(α-Syn PFF).Methods SH-SY5Y cells were divided into undifferentiated and RA-differentiated groups.The expression levels of tyrosine hydroxylase(TH),dopamine transporter(DAT),lymphocyte activation gene 3(LAG3),and Nestin proteins in the cells were detected using Western blotting,whereas those of microtubule-associated protein 2(MAP2)and neu-ronal nuclei(NeuN)were detected using immunofluorescence staining.Furthermore,RA-treated SH-SY5Y cells were divided into control and α-Syn PFF groups,and their levels of chromatin condensation were detected using Hoechst 33342 staining.Nitric oxide(NO)levels were measured using a NO assay kit.Additionally,the protein levels of TH,poly(ADP-ribose)(PAR),and poly(ADP-ribose)poly-merase(PARP)in these cells were detected using Western blotting,whereas their expression levels of phosphorylated α-Syn(pS129-α-Syn)and phosphorylated histone H2AX(γH2AX)were detected using immunofluorescence staining.Results Treatment with RA resulted in a reduction in cell body size and the elongation of protrusions in SH-SY5Y cells.The results of Western blotting showed that RA treatment could increase the TH,DAT,and LAG3 levels and decrease the Nestin level in SH-SY5Y cells(P＜0.05).α-Syn PFF treat-ment decreased the TH protein level and increased the PAR,PARP-l,and cleaved PARP-1 levels in differentiated SH-SY5Y cells(P＜0.05).According to the immunofluorescence results,RA treatment increased the expression levels of MAP2 and NeuN in SH-SY5Y cells(P＜0.001).The α-Syn PFF treatment increased the expression levels of γH2AX and pS129-α-Syn in RA-differentiated SH-SY5Y cells(P＜0.01).The Hoechst 33342 staining results showed that α-Syn PFF treatment led to chromatin condensation in the differentiated SH-SY5Y cells(P＜0.001)and increased the NO levels(P＜0.01).Conclusion A cellular model of Parkinson disease can be established by treating RA-differentiated SH-SY5Y cells with α-Syn PFF.

Objective:To explore the safety and efficacy of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating painful chronic pancreatitis patients with pancreatic stones.Methods:The painful chronic pancreatitis patients receiving P-ESWL alone or P-ESWL combined with ERCP at Shanghai Pudong New Area Gongli Hospital from August 2019 to December 2021 were retrospectively analyzed. The success rate of stone fragmentation following P-ESWL, occurrence of postoperative complications, stone clearance rate of the main pancreatic duct and degree of pain relief in the follow-up were evaluated.Results:Among 113 patients, 7 patients were treated with P-ESWL alone and 106 patients were treated by P-ESWL combined with ERCP. The success rate of stone fragmentation was 98.2%. The occurrence of P-ESWL complications was 6.2%. Complete clearance of the main pancreatic duct stones was achieved in 75.2% of patients. With the mean follow-up of 17.5(3-31) months, complete pain relief was achieved in 84.1% of patients. The pain frequency and VAS score of patients treated with P-ESWL alone and P-ESWL combined with ERCP were obviously lower than those before treatment, and the body weight and body mass index were significantly higher than those before treatment, all with statistically significant differences (all P value <0.01). Conclusions:P-ESWL is safe and effective for the management of painful chronic pancreatitis patients with main pancreatic duct stones.

Objective:To explore the clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the direction of head and foot.Methods:Twenty-eight patients who presented Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from January 2017 to June 2019 were collected. All patients who underwent one-step CT angiography of the deep veins of the lower extremities to the pulmonary artery were randomly divided into two groups, A or B, and scanned from the entrance of the thorax to 10 cm below the knee joint. Group A was foot-head direction group with delayed time scanning according to empirical method. Group B was the head-foot direction group with a single point triggered automatic tracing scan at the level of the main pulmonary artery trunk. The independent sample t-test was used to compare the scan time, dose length product (DLP), and mean CT value of enhancement of the pulmonary artery opening between the two groups. Results:The average scanning time of the foot-head scanning group was (36.4±1.2)s, the average DLP was (684.4±37.8) mGy·cm, and the average enhanced CT value of pulmonary artery image was (181.3±15.5) HU. The average scanning time of the head foot scanning group was (16.4±0.3) s, the average DLP was (441.8±34.4) mGy·cm, and the average enhanced CT value of the pulmonary artery image was (257.9±24.5) HU. Scanning time, mean DLP, and pulmonary artery level enhancement values were significantly different between the two groups ( t=17.92, 4.71, 2.44, P<0.05). Conclusions:The clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the head-foot direction is significantly better than that in the head-foot direction. It can significantly shorten the scanning time, reduce the radiation dose, and increase the enhancement value of pulmonary artery to improve the detection of pulmonary embolism.

Objective:To summarize our institutional experiences of screening and selecting potential recipients and living donors for uterine transplantation at a single center.Methods:A total of 102 patients were diagnosed as absolute uterine factor infertility (AUFI). Depending upon the outcomes of previous trials, 8 modules were selected for surveying. A registration form was distributed for subjects at outpatient clinics or through telephone consultations for clinical trials of uterus transplantation between November 2018 and October 2019. The relevant information was collected and entered into a dedicated system for data processing.Results:The number of eligible subjects was 84 and the number of recipients with potential donors 37. The average age of potential recipients was 26.0(18-47) years. Among potential recipients, 76(90.5%) had congenital AUFI and 8(9.5%) acquired AUFI. For potential donors with available organs, the average age was 47.5(32-64) years and the proportion of menopausal or peri-menopausal status 56.8%.Conclusions:Currently large demands and sufficient supports for conducting clinical trials of uterine transplantation are available in China. However, inherent deficiencies persist in organ donor population reserves and preoperative screening protocols, such as donor age and subjective/objective factors of participants. During clinical trials of uterine transplantation, preoperative screening should be performed for expanding the screening scope, extending the screening time and popularizing the screening knowledge to boost the success rate.

Objective To analyze the optimal timing of endoscopic stone extraction combined with extracorporeal shock wave lithotripsy (ESWL) in the treatment of chronic pancreatitis (CP) with pancreatic stones. Methods Data regarding 170 pancreatic stone patients receiving ESWL and endoscopic stone extraction at Shanghai Changhai Hospital from February 2014 to February 2015 were retrospectively analyzed. Based on the the prior history of endoscopic treatment,patients were divided into group A and B,and then sub-divided into three groups according to the timing of endoscopic intervention after ESWL including <12 h,12~36 h and >36 h subgroup. The success of pancreatic ductal cannulation, clearance of stone in the main pancreatic duct, and ERCP-related complications were evaluated. Results Among all the enrolled 170 patients,107 previously received ERCP(group A) while the others didn't(group B). The overall success rate of cannulation and clearance rate of stones at different times showed no significant difference. The success rate and clearance rate in group A in <12 h,12~36 h and >36 h subgroup were 91.7%,95.2%,78.0%,and 91.7%,95.2%,80.0%,and no significant difference existed. In group B, the success rate and clearance rate in <12 h, 12~36 h and >36 h subgroup were 66.7%, 71.4%, 96.3%, and 60.0%, 76.2%, 92.6%, and the differences were statistically different. The success rate and clearance rate of >36 h subgroup in group B were obviously higher than that in <12 hours (P=0.025) and 12~36 h subgroup (P=0.04). The timing of endoscopic stone extraction did not influence ERCP-related complications. Conclusions Early endoscopic stone extraction after ESWL can be considered in patients with pancreatic stones who previously underwent ERCP. Delayed endoscopic stone extraction after ESWL is recommended in patients without prior ERCP,which can help promote the therapeutic efficacy.

BACKGROUND:Macropore morphology of a composite scaffold prepared by the three-dimensional printing technique is of great importance in determining the physicochemical and biological properties of tissue engineering scaffolds.OBJECTIVE:To fabricate strontium-containing mesoporous (Sr-MBG) bioactive glass (PCL) scaffolds by the three-dimensional printing technique, and to explore the effect of these scaffolds on MC3T3-E1 proliferation and osteogenic differentiation, thereby to find out the optimal macropore morphology.METHODS: Sr-MBG/PCL composite scaffolds were fabricated by the three-dimensional printing technique. The angles between fibrous latitudes and longitudes were set to 45°, 60° and 90°. Then the proliferation and alkaline phosphatase activity of MC3T3-E1 cells on the scaffolds were tested.RESULTS AND CONCLUSION: Cell counting kit-8 results showed that MC3T3-E1 cells could proliferate on all the three kinds of scaffolds. The proliferation rate of MC3T3-E1 cells on the 45° Sr-MBG/PCL scaffolds was just slightly higher than that on the 60° and 90° Sr-MBG/PCL scaffolds at days 1 and 4 (P > 0.05), but there was a significant increase at day 7 (P < 0.05). The 45° Sr-MBG/PCL scaffolds exhibited a significant increase in alkaline phosphatase activity of MC3T3-E1 cells compared to the 60° and 90° Sr-MBG/PCL scaffolds at day 14 (P < 0.05), while there was no significant difference among three groups at day 21 (P > 0.05). These results indicate that the 45° Sr-MBG/PCL scaffold is more suitable to promote the proliferation and osteogenic differentiation of the MC3T3 cells than the 60° and 90° Sr-MBG/PCL scaffolds.

BACKGROUND:Artificial hip replacement by the posterolateral approach is generally introduced as a treatment for femoral neck fracture in the elderly, but it is limited by the need for a large incision, cutting off the extortor, and postoperative hip dislocation. The supercapsular percutaneously-assisted total hip (SuperPATH) approach was developed based on the original lateral approach. The SuperPATH approach for hip replacement is characterized by the reduced chance of damaging blood vessels and nerves, reducing intraoperative blood loss, retaining all the joint capsules and supinator, and significantly reducing the incidence of postoperative hip dislocation. OBJECTIVE:We hypothesized that the SuperPATH approach for hip replacement can achieve better efficacy in the elderly with femoral neck fractures and promote the recovery of postoperative hip function compared with the posterolateral approach. METHODS/DESIGN:This is a prospective, single-center, open-label, randomized control ed clinical trial that will be completed at the Pudong Hospital of Fudan University, Shanghai, China. Forty patients with femoral neck fractures were randomly divided into two groups to undergo femoral head replacement by the SuperPATH approach in the experimental group, and by the conventional posterior approach in the control group. The follow-up period is 1 week and 6 months. The main outcome measures are Harris hip scores at baseline, and at 1 week and 6 months postoperatively to assess functional recovery of the hip. Secondary outcome measures to evaluate the advantages of the SuperPATH approach include the length of surgical incision, intraoperative blood loss, operative time, 24-hour postoperative drainage, and hospital stay. Other outcome measures include the incidence of adverse reactions at 1 week and 6 months after surgery. The study protocol was approved by the Ethics Committee of the Pudong Hospital of Fudan University, China, and performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Written informed consent was obtained from all participants. DISCUSSION:The aim of this trial is to test our hypothesis that the SuperPATH approach is safer and more reliable for hip functional recovery compared with the posterolateral approach for the artificial hip replacement in femoral neck fractures of the elderly.