Objective To investigate the mechanism by which apelin inhibits the transition from acute kidney injury(AKI)to chronic kidney disease(CKD).Methods Human proximal tubular epithelial cells were cultured in vitro and divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 siRNA,and apelin groups.Cells were transfected with Sirt3 siRNA and incubated with a medium containing cisplatin(10 μmol/L)and/or apelin-13(1 μmol/L).Mitochondrial morphology was observed using MitoTracker? probes;mito-chondrial membrane potential was detected using the JC-1 assay kit;and the expression of the fibrogenic cytokine,transforming growth factor β1(TGF-β1)was measured by Western blotting.Forty 10-week-old male C57BL/6J mice were divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 knockdown,and empty adenovirus groups,with eight mice per group.Except for the control and empty adenovirus groups,all the other groups were intraperitoneally injected with cisplatin(20 mg/kg)to establish the AKI model.The cis-platin+apelin group was intraperitoneally injected with apelin-13(0.1 μg·kg-1·d-1);the control group was injected with an equal volume of saline;the cisplatin+apelin+Sirt3 knockdown group was injected with Sirt3 knockdown adenovirus(2 × 109 pfu/mL)via the tail vein and intraperitoneal injection of apelin-13(0.1 μg·kg-1·d-1);and the empty adenovirus group was injected with adenovirus(2 × 109 pfu/mL)via the tail vein.The mice were sacrificed after 2 weeks.Kidney fibrosis was assessed by Masson's trichome staining.Type Ⅰ collagen(Col-Ⅰ)expression was observed by immunohistochemical staining.Plasma creatinine(Cr)and blood urea nitrogen(BUN)levels were measured by ELISA.Results In vitro experiments showed that,compared with the control group,the cisplatin group exhibited reduced mitochondrial fluorescence staining,decreased mitochondrial membrane potential,and increased TGF-β1 expression(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed increased fluorescence staining,elevated mitochondrial membrane potential,and reduced TGF-β1 expression(all P＜0.05);however,these effects were counteracted after Sirt3 siRNA transfection.In vivo experiments showed that,compared with the control group,the cisplatin group exhibited significant renal tubular atrophy and interstitial fibrosis,increased Col-Ⅰ positive expression,and elevated plasma Cr and BUN levels(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed a significant improvement in all the above indicators(all P＜0.05).Compared with the cisplatin+apelin group,the cisplatin+apelin+Sirt3 knockdown group showed a significant reduction in the renal protective effects of apelin.Conclusion The polypeptide apelin inhibits the transition from AKI to CKD by regulating Sirt3 expression to maintain mitochondrial structure and function,which can reduce renal fibrosis and improve renal function.

The presence of magnetic fields in a magnetic resonance accelerator (MR-linac) can affect the reference dosimetry, and thus the existing Code of Practices (CoPs) are inadequate for MR-linac. In this article, the characteristics of adsorbed dose to water and ionization chamber response in the presence of magnetic fields were introduced and a formalism for reference dosimetry in MR-linac was developed based on the existing CoPs, aiming to provide reference for dosimetric quality control and research work of MR-linac in China.

Objective To investigate the mechanism by which apelin inhibits the transition from acute kidney injury(AKI)to chronic kidney disease(CKD).Methods Human proximal tubular epithelial cells were cultured in vitro and divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 siRNA,and apelin groups.Cells were transfected with Sirt3 siRNA and incubated with a medium containing cisplatin(10 μmol/L)and/or apelin-13(1 μmol/L).Mitochondrial morphology was observed using MitoTracker? probes;mito-chondrial membrane potential was detected using the JC-1 assay kit;and the expression of the fibrogenic cytokine,transforming growth factor β1(TGF-β1)was measured by Western blotting.Forty 10-week-old male C57BL/6J mice were divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 knockdown,and empty adenovirus groups,with eight mice per group.Except for the control and empty adenovirus groups,all the other groups were intraperitoneally injected with cisplatin(20 mg/kg)to establish the AKI model.The cis-platin+apelin group was intraperitoneally injected with apelin-13(0.1 μg·kg-1·d-1);the control group was injected with an equal volume of saline;the cisplatin+apelin+Sirt3 knockdown group was injected with Sirt3 knockdown adenovirus(2 × 109 pfu/mL)via the tail vein and intraperitoneal injection of apelin-13(0.1 μg·kg-1·d-1);and the empty adenovirus group was injected with adenovirus(2 × 109 pfu/mL)via the tail vein.The mice were sacrificed after 2 weeks.Kidney fibrosis was assessed by Masson's trichome staining.Type Ⅰ collagen(Col-Ⅰ)expression was observed by immunohistochemical staining.Plasma creatinine(Cr)and blood urea nitrogen(BUN)levels were measured by ELISA.Results In vitro experiments showed that,compared with the control group,the cisplatin group exhibited reduced mitochondrial fluorescence staining,decreased mitochondrial membrane potential,and increased TGF-β1 expression(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed increased fluorescence staining,elevated mitochondrial membrane potential,and reduced TGF-β1 expression(all P＜0.05);however,these effects were counteracted after Sirt3 siRNA transfection.In vivo experiments showed that,compared with the control group,the cisplatin group exhibited significant renal tubular atrophy and interstitial fibrosis,increased Col-Ⅰ positive expression,and elevated plasma Cr and BUN levels(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed a significant improvement in all the above indicators(all P＜0.05).Compared with the cisplatin+apelin group,the cisplatin+apelin+Sirt3 knockdown group showed a significant reduction in the renal protective effects of apelin.Conclusion The polypeptide apelin inhibits the transition from AKI to CKD by regulating Sirt3 expression to maintain mitochondrial structure and function,which can reduce renal fibrosis and improve renal function.

The presence of magnetic fields in a magnetic resonance accelerator (MR-linac) can affect the reference dosimetry, and thus the existing Code of Practices (CoPs) are inadequate for MR-linac. In this article, the characteristics of adsorbed dose to water and ionization chamber response in the presence of magnetic fields were introduced and a formalism for reference dosimetry in MR-linac was developed based on the existing CoPs, aiming to provide reference for dosimetric quality control and research work of MR-linac in China.

Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.

Objective:To explore the feasibility of applying ArcherQA to independent dose verification of MR-guided online adaptive radiotherapy (ART) plans performed on Elekta Unity 1.5 Tesla (T) magnetic resonance-linear accelerator (MR-Linac).Methods:The dose calculation accuracy of ArcherQA under a specific magnetic field was validated using a homogeneous water phantom. A total of 32 patients who received MR-guided online ART on Elekta Unity were randomly selected by lottery, with 32 offline plans and 177 online plans for five treatment sites (brain, mediastinum, liver, kidney, and vertebral body) enrolled. Finally, the γ pass rates (threshold: 10%; criteria: 3 mm/3% and 2 mm/2%) were compared among the result upon independent dose verification of ArcherQA, measurements of ArcCheck, and calculations using the Monaco treatment planning system (TPS) to quantitatively evaluate the accuracy and efficiency of ArcherQA in independent dose verification of online plans on Elekta Unity.Results:ArcherQA was proven accurate in calculating the dose distribution of therapeutic photon beams under the specific magnetic field. With the 3 mm/3% criterion, the γ pass rates of verification result exceeded 99% in all square fields of a water phantom. Under the stricter 2 mm/2% criterion, the γ pass rates also surpassed 95% in all square fields except 20 cm × 20 cm field. Regarding the verification of treatment plans, the ArcherQA result were found to be highly consistent with those measured or calculated using ArcCheck and Monaco TPS, with the average γ pass rates exceeding 99% under the 3 mm/3% criterion and above 97% under the 2 mm/2% criterion. ArcherQA was acceptably efficient for independent dose verification of online plans, with 50 to 150 s, (108 s on average) required to complete the independent dose verification of 177 online plans.Conclusions:ArcherQA allows for accurately and efficiently calculating the dose distribution of therapeutic photon beams under a specific magnetic field, establishing it as an effective supplementary tool for independent dose calculation of MR-guided offline and online ART plans, thereby ensuring the safety of patient treatment plans.

Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms.Methods Human renal podocytes were divided into four experimental groups:control group,high glucose(HG)group(glucose 25 mmol/L,48 h),Apelin intervention HG group(Ape-lin-13 1 μmol/L,48 h)and Apelin group(Apelin-13 1 μmol/L,48 h).The podocyte apoptosis was observed by TUNEL staining,the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot,and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation.The 8-week-old male mice were divided into three experimental groups:control group,diabetes group(intraperito-neal injection of streptozotocin 150 mg/kg,only one time)and Apelin intervention DM group(intraperitoneal injection of Apelin-13 0.3 μmol/kg,daily).The morphology of renal was observed by PAS staining and trans-mission electron microscopy.Plasma creatinine(Cr),urea nitrogen,urinary albumin and creatinine were de-tected by ELISA kit.The level of creatinine clearance rate(Ccr)and urinary albumin/creatinine(ACR)was calculated.Results Compared with the control group,the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly(P＜0.05),and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised.Meanwhile,compared with the HG group,the number of apoptosis,the expression of FUNDC1(P＜0.05),and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group.Animal experiments showed that the kidney structure of the control group was intact.In the DM group,the num-ber of podocytes decreased significantly,the foot processes were fused and dropped off.In the Apelin intervention DM group,podocyte lesions were less severe than those in the DM group.Compared with the control group,the level of plasma Cr,BUN and urine ACR in the DM group increased,while the level of Ccr decreased significantly(P＜0.05).However,compared with the DM group,the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte ap-optosis by inhibiting the expression of mitochondrial membrane protein FUNDC1,which may contribute to allevia-tion of diabetic nephropathy.

Objective:To analyze the dosimetric effects on off-center tumour treatment plan resulting from the MR-Linac-based isocenter position radiotherapy plan.Methods:The cases of 19 patients who were treated in Sun Yat-sen University Cancer Center in 2020 were collected in this study. Two different IMRT plans were designed for each patient with off-center tumor both for group A with planned isocenter position as IMRT and group B with planed target center position as geometric center. The conformity index and homogeneity index of target, the dose normal tissue and the number of MU were compared between two plans.Results:The two IMRT plans met clinical dosimetric requirements. No statistical differences were found both in homogeneity index and conformity index ( P>0.05). Also there was no differences found in doses to normal tissues. However, the MU number (1 149±903, t=2.804, P=0.012) in group A was higher than that in group B (970±652). Conclusions:It is feasible to perform MR-Linac-based off-center treatment plan.

Objective:To investigate the feasibility of applying the ArcherQA three-dimensional (3D) dosimetric verification system in intensity-modulated radiotherapy (IMRT) plans for nasopharyngeal carcinoma (NPC).Methods:A retrospective analysis was conducted for 105 NPC patients′ IMRT plans developed using the Eclipse treatment planning system (TPS). Dose verification was conducted using the ArcherQA system and through portal dosimetry (PD). Moreover, this study compared γ passing rates (criteria: 3 mm/3%, TH = 10%) between ArcherQA and PD and the doses delivered to the target volume ( Dmean, D90%) and organs at risk (OARs) ( Dmean) between ArcherQA and TPS, and analyzed the 3D γ passing rates of each organ at risk calculated by ArcherQA. Results:The average 3D γ passing rate calculated by ArcherQA was (99.04±1.01)%, and the average 2D γ passing rate measured by PD was (99.49±0.78)%, with statistically significant differences ( t=-3.35, P< 0.05). The dosimetric differences to the target volume between ArcherQA and TPS were as follows: the average difference in Dmean to the gross tumor volume (GTV) was (0.57±0.48)%, and the average difference in D90% was (0.65±0.56)%. For the target volume, the average γ passing rate was (97.67±3.43)% for GTV, (97.80±4.35)% for GTVnd-L, (97.82±4.07)% for GTVnd-R, (97.88±2.44)% for CTV1, and (96.64±4.32)% for CTV2. The mean dose difference of each target volume was CTV1 (0.57±0.46)%, GTVnd-L (0.85±0.55)%, GTVnd-R (0.73±0.55)%, and CTV2 (0.88±0.52)%. For OARs, the mean γ passing rate was (99.93±0.22)% for the brainstem, (99.17±2.82)% for the optic chiasm, (100±0)% for the lens, (99.56±1.05)% for the spinal cord, (99.00±2.06)% for the thyroid, and (87.86±10.42)% for the trachea. Statistically significant differences in the average doses to OARs were observed ( t=-14.62 to 4.82, P<0.05), except for those to the left optic nerve, the right hippocampus, and the right parotid gland. Conclusions:Based on the high-performance GPU platform and the Monte Carlo dose algorithm, ArcherQA can provide accurate 3D dose distribution and 3D γ passing rates inside patients according to CT images and provide the dose volume histogram (DVH) of various regions of interest (ROIs). Therefore, the ArcherQA three-dimensional dose verification system can be applied to IMRT plans for NPC. Moreover, it is inducive to improve the treatment efficiency since it does not occupy the accelerator operation time.