Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Objective:To investigate the efficacy and adverse effects of combination therapy containing venetoclax in the treatment of t(11; 14) plasma cell disorders.Methods:A retrospective case series study was conducted. The clinical data of plasma cell disorders patients with t(11; 14) treated with combination therapy containing venetoclax in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 2020 to September 2023 were collected. The general data included baseline clinical characteristics, treatment regimens, treatment responses, survival, and adverse events. The duration of orally administered venetoclax-based treatment regimen was 28 d, and the dose of venetoclax was appropriately adjusted according to the tumor burden and general conditions of patients. Patients were grouped according to drug dosage and treatment regimen. The overall survival (OS) analysis was performed by using Kaplan-Meier method and log-rank test was used for comparison among groups.Results:Among the 14 plasma cell disorders patients with t(11;14), 13 had multiple myeloma (MM) and 1 had primary plasma cell leukemia (pPCL). The median time [ M ( Q1, Q3)] from initial diagnosis to venetoclax treatment was 21 months (8 months, 39 months). The median number of therapy lines was 2 (1, 4); 7 patients had drug resistance to both proteasome inhibitors (PI) and immunomodulators (IMiD), and 5 patients had drug resistance to PI, IMiD and anti-CD38 monoclonal antibodies; 2 patients died after 1 uncompleted course of treatment and they were not enrolled into efficacy evaluation and survival analysis. Among the 11 MM patients evaluable for treatment response, 6 achieved at least partial remission (PR). Of the 4 patients who received the first-line or second-line therapy containing venetoclax, 2 achieved strict complete remission (sCR), 1 achieved very good partial remission (VGPR), and 1 achieved PR. The median course number of therapy lines with venetoclax was 2 (2, 6), and the median acting time was 1.1 months (0.75 months, 1.75 months). Until the last follow-up in May 2024, the median duration of remission of 11 MM patients was 3.3 months (95% CI: 0-7.1 months), and the median OS time was 22.7 months (95% CI: 0-52.5 months). The median OS time was 9.6 months, 31.2 months, respectively in venetoclax combined with PI group (6 cases) and venetoclax combined with daratumumab (Dara) group (4 cases), and the difference in OS between the 2 groups was statistically significant ( P = 0.093); the median duration of remission was 1.7 months and 9.8 months, respectively in venetoclax combined with PI group and venetoclax combined with Dara group, and the difference was statistically significant between the 2 groups ( P = 0.025). The median OS time in high-dose group (maximum dose of venetoclax ≥300 mg, 6 cases) and low-dose group (maximum dose of venetoclax < 300 mg, 5 cases) was 31.2 and 7.5 months, respectively, and the difference in OS was statistically significant ( P = 0.013). The median duration of remission was 9.8 months, 1.6 months, respectively, and the difference was statistically significant ( P = 0.048). Grade ≥3 adverse events of 11 MM patients included neutropenia, lymphopenia, infection, thrombocytopenia, and hypokalemia; 6 patients experienced grade ≥3 adverse events, 2 patients discontinued treatment due to adverse events, and no treatment-related deaths occurred. The pPCL patient received 5 courses of treatment with venetoclax plus DECP (cisplatinum + etoposide + cyclophosphamide + dexamethasone) induction therapy followed by chimeric antigen receptor T cell therapy and then continued venetoclax maintenance, achieving sCR with the duration remission of 18.7 months. During induction, the patient experienced grade 3 neutropenia and infection. Conclusions:The combination therapy containing venetoclax is safe and manageable in MM patients with t(11; 14) and pPCL. The patients receiving early, regular, and adequate-dose treatment with venetoclax have better therapeutic efficacy.

Chimeric antigen receptor T-cell (CAR-T) immunotherapy targeting B-cell maturation antigen (BCMA) has shown significant efficacy in relapsed/refractory multiple myeloma. With the rapid development of CAR-T therapies, CAR-T therapies targeting BCMA continue to be optimized, and new products such as new targets, dual-targets and universal CAR-T are arriving successively. Data from several relevant clinical studies were updated at the 64th American Society of Hematology Annual Meeting.

Objective:To evaluate the volumetric modulated arc therapy (VMAT) dose verification of cervical cancer based on γ rule and dose volume histogram (DVH) and to perform correlation analysis between the evaluation results and the dose differences.Methods:Twenty cervical cancer VMAT plans were selected and performed on TrueBeam Linac. The delivered point and surface dose was measured by FC-65 G and ArcCheck and the results were compared to those calculated by Eclipse. The dose of patients was reconstructed by 3DVH. Then, differences between the reconstructed and plan value of D mean, D 95%, D 98% and D 2% of PTV, V 20Gy of left and right femoral head, V 40Gy of rectum, D 1cm 3 of cord, D 98%, D 2% and D 50% of the 50% prescription iso-dose volume (IDV), were evaluated and 3-dimensional (3D) γ was assessed for each organ. Lastly, Pearson’s correlation coefficient was used to analyze the relationship between point dose difference, 2D γ pass-rate (γ%), γ mean and 3D γ% of each organ and the dose difference. Results:Small differences were found between the point dose measured, reconstructed and the plan value. Differences between D mean of PTV, all dose parameters of IDV and plan values were all within 3% and V 40Gy of rectum showed the largest difference. As for the 3D γ%, the maximum pass rate was found for the left and right femoral head and the maximum variance for cord D 1cm 3. There was a moderate correlation between measured and reconstructed point dose deviation and dose difference of each organ, while no significant correlation was found for 2D γ%. Strong correlation was found between 3D γ% of target and D 50% of PTV/IDV and no correlation was found for other organs. Conclusion:The performance of both γ-and DVH-based evaluation can reveal dose error for dose verification, but both of them have some limitations and should be combined in clinical practice.

Objective:To investigate the advantages of Da Vinci robotic thyroidectomy in treatment of the unilateral papillary thyroid microcarcinoma (PTMC).Methods:The clinical data of 49 patients with unilateral thyroid cancer admitted to the First Hospital of Shanxi Medical University from June 2018 to March 2020 were retrospectively analyzed, and they were divided into Da Vinci robotic group (the experimental group, 18 cases) and conventional surgery group (the control group, 31 cases) according to the surgical method. The clinicopathological characteristics, perioperative and postoperative related indexes changes, length of hospital stay, incidence of surgical complications, and operation cost of both groups of patients were analyzed. Visual analogue scale (VAS) was used to evaluate postoperative pain.Results:There were statistically significant differences in age, marriage and education background of both groups (all P < 0.05). There were statistically significant differences in the number of central lymph node dissection [(4.3±2.0) vs. (6.5±3.9)], operation time [198.5 min (166.3 min, 228.5 min) vs. 82.0 min (60.0 min, 102.0 min)], pain score of 24 h after surgery [3 scores (3 scores, 4 scores) vs. 2 scores (2 scores, 3 scores)], postoperative total drainage volume [49.0 ml (40.8 ml, 56.5 ml) vs. 37.0 ml, (29.0 ml, 44.0 ml)], operation cost [33,200 yuan (33,100 yuan, 34,000 yuan) vs. 5,200 yuan (4,200 yuan, 5,900 yuan)], and differences were statistically significant (all P < 0.05). No postoperative complications such as hemorrhage, fat liquefaction and subcutaneous ecchymosis occurred in all patients of the two groups. Conclusion:Da Vinci robotic thyroidectomy is safe and reliable in treatment of the unilateral PTMC, and it has good therapeutic effects.

Objective:To study the changing characteristics and impact factors of helical tomotherapy (HT)for longitudinal dose fall-off outside the target, in order to guide the plan junction or pretreatment target and implementation efficiency in clinical.Methods:Eight patients with head and neck tumors admitted to the Department of Oncology Radiotherapy of the First Affiliated Hospital of Zhengzhou University in December 2019 were retrospectively selected as the research objects. The planning target area and dose drop structure were outlined in the head and neck images with a thickness of 1 mm obtained by Siemens SOMATOM Definition AS positioning computerized tomography (CT). Different field widths (FW, 5.0 cm/2.5 cm/1.0 cm) and pitches (0.430/0.287/0.215) were assembled for planning with the same modulation factor (1.8), finest does calculation grid (0.195 cm ×0.195 cm) and other planning parameters were consistent. The plans were designed by different parameters, and the result was analyzed by univariate analysis.Results:The that different pitch curves coincided under the same field width by comparative analyzing, so pitchs had no effect on dose drop. The different field width curves were independent of each other, indicating that the field width had an effect on dose drop in the head and foot direction. The relationship between the longitudinal dose drop speed outside the target and the change of the field width was inversely correlated: the larger field widths meant the slower dose fall-off and the larger penumbra, while the smaller field widths meant the faster fall-off and the smaller penumbra. When the dose fall-off to 50% of the prescribed dose, the distance from the target was approximately equal to half the field widths, and the pitchs had not affect the rate of dose-drop, while the dose at different distances from the target boundary could be calculated by the fitting formulas. The field widths and pitchs had little effect on the CI and HI index of the target, relatively, the target area was best when the field width was 2.5 cm. The total beam-on time gradually decreased with the increase of the field widths and pitches.Conclusions:When segment target therapy needs to consider planning junction, execution efficiency, and controlling longitudinal dose fall-off and considered the execution, the optimal planned parameters such as field widths and pitches could be selected or the target at the junction regions could be adducted according to the longitudinal dose drop formula, so as to achieve the ideal dose distribution.

Objective:To compare and investigate the effects of laparoscopy and open colorectal cancer on the intestinal barrier function in patients with colorectal cancer.Methods:Sixty-two patients with colorectal cancer admitted in our hospital from January 2015 to October 2016 were selected and divided into laparoscopic surgery group with thirty-four patients and open surgery group with twenty-eight patients. The changes of postoperative intestinal barrier function were compared between the two groups.Result:The levels of plasma D-lactate, plasma diamine oxidase (DAO) and bacterial endotoxin in the laparoscopic surgery group were significantly lower than those in the open surgery group ( P<0.05). Conclusion:Laparoscopic and open colorectal cancer surgery can cause damage to intestinal barrier function, but the damage of laparoscopic colorectal cancer surgery is lower than that of open colorectal surgery.

Objective: To achieve quantitative analysis of image quality parameters and establish warning and action thresholds for the on-board imaging (OBI) system of linear accelerator. Methods: The Catphan604 phantom was repeatedly scanned in the Full-Fan and Half-Fan CBCT scanning modes on a Varian EDGE linear accelerator, and the software based on Python language development in-house was utilized to analyze image quality parameters, such as CT number linearity, geometric consistency, slice thickness, spatial resolution, uniformity and low-contrast resolution. The quantitative analysis results of each image quality parameter obtained from 16 times of scanning within 16 months were normalized to the mean and the standard deviations were recorded. A run chart analysis was created to determine the warnings and action thresholds. Results: The software built in-house can quantitatively analyze the image parameters of the two scanning modes of OBI system. The low-contrast resolution of Half-Fan was better than that of Full-Fan, whereas the spatial resolution of Full-Fan was superior to that of Half-Fan. One standard deviation (1σ) was set as the warning threshold and 2 standard deviations (2σ) as the action threshold, respectively. The tolerance level of Half-Fan was smaller than that of Full-Fan. Conclusion Self-developed software enables quantitative analysis of accelerator image quality parameters, establishes warning and action tolerance of quality assurance and provides guidance for image quality assurance under image-guided radiotherapy specification.

Objective To investigate the application value of three-dimensional (3D) reconstruction virtual surgery planning in the surgical treatment of hilar cholangiocarcinoma.Methods The retrospective crosssectional study was conducted.The clinical data of 36 patients with hilar cholangiocarcinoma who were admitted to the First Affiliated Hospital of Fujian Medical University between January 2014 and September 2017 was collected.Before operation,images of 3D virtual surgery planning were respectively reconstructed and determined using IQQA-Liver imaging analysis system,and then precise resection of tumor was performed based on results of virtual surgical planning and intraoperative conditions.Observation indicators:(1) virtual surgical planning;(2) surgical and postoperative situations;(3) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival and tumor recurrence or metastasis up to November 2017.Measurement data with normal distribution were represented as (x)±s.Comparison between indicator of preoperative virtual surgical planning and surgical indicators was analyzed by the t test.The postoperative survival time was calculated by the Kaplan-Meier method.Results (1) Virtual surgical planning:36 patients accomplished 3D visualization reconstruction and virtual surgical planning.Three D visualization reconstruction clearly showed adjacent relationship between tumor size and surrounding vessels or bile duct space.Type Ⅱ,Ⅲ a,Ⅲb and Ⅳ of Bismuth-Corlette Classification were detected in 2,13,14 and 7 patients by 3D visualization system,respectively.The tumor volume,whole liver volume,predicted liver resection volume and remnant liver volume were respectively (76± 26) mL,(1 319± 306) mL,(588± 128) mL and (731± 269) mL.(2) Surgical and postoperative situations:of 36 patients,16,12,5 and 3 patients underwent left hemigepatectomy,right hemigepatectomy,extended left hemigepatectomy and extended right hemigepatectomy,respectively,and all of them were combined with caudate lobectomy of liver.Combined resection and reconstruction of hepatic artery,combined wedge resection and repair of the portal vein and combined end-to-end anastomosis after resection of the portal vein were detected in 1,2 and 1 patients,respectively.Operation time and volume of intraoperative blood loss of 36 patients were respectively (368± 134)minutes and (474±288)mL.Thirty-six patients with postoperative complications were cured by conservative treatment,including 3 with pulmonary infection,3 with intra-abdominal infection and 2 with intra-abdominal lymphatic fistula.Duration of hospital stay of 36 patients was (19±7) days.Type Ⅱ,Ⅲ a,Ⅲ b and Ⅳ of postoperative Bismuth-Corlette Classification were detected in 2,11,13 and 10 patients,respectively.Accuracy of tumor classification through 3D visualization reconstruction was 91.7％ (33/36).Actual liver resection volume of 36 patients was (551± 141)mL,and was not significantly different from predicted liver resection volume (t =1.148,P＞0.05).(3) Follow-up and survival:31 of 36 patients were followed up for 2-39 months after surgery,with a median time of 16 months.The postoperative median survival time was 13 months,and 9 patients had tumor recurrence or metastasis during the follow-up.Conclusion The 3D reconstruction virtual surgery planning can accurately complete the preoperative evaluation,meanwhile,it can also provide important reference for the surgical therapy of hilar cholangiocarcinoma.

Objective To investigate the optimal distance between upper and lower target volumes and their correlated planning parameters by analyzing the dose distribution in the abutment regions during total body irradiation ( TBI) using helical tomotherapy. Methods A total of 10 patients with acute leukemia and with a height around 120 cm were enrolled. All patients were scanned by a Siemens simulation computerized tomography (CT) at a slice thickness of 5 mm. A lead wire was placed 10. 0 cm above the patella as a marker of the separation boundary for the upper and lower target volumes. The delineations of target volumes and organs at risk ( OARs ) were performed in the Varian Eclipse 13. 5 workstation with targets shrunk beyond the separation boundary at different distances. After contours and CT images were transferred to HT workstation, treatment plans were designed with different field width (FW, 5. 0 cm/2. 5 cm/1. 0 cm) and pitch values (0. 430/0. 287) at a modulation factor of 1. 8. All the plans were optimized with a dose calculation grid of 0. 195 cm × 0. 195 cm and identical planning parameters. The correlation between treatment planning parameters and targets shrunk distances were investigated by analyzing the dose distributions in the abutment area. Results The study demonstrated that the dose distributions in the abutment area were influenced only by the field width parameters: when the gap distance between the upper and lower targets was 5. 0 cm, the optimal FW is 5. 0 cm;Similarly when the gap distances were 2. 0 cm and 1. 0 cm, and the optimal FW 2. 5 cm and 1. 0 cm, respectively. In another words, the dose distribution of the abutment region was optimal when the target gap distance was equal to FW. Pitch values did not affect the quality of dose distribution in the abutment region and the overall treatment time ratio. Overall treatment time was inversely related to the FW. Conclusions Consistent target distance and FW is helpful to improve the dose homogeneity in the abutment area during TBI with HT. Appropriate planning parameters is critical to balance the treatment efficacy and efficiency.