Objective:To investigate the effect of the transcription factor TBX1 on the proliferation of colorectal cancer cells and to explore potential molecular mechanisms.Methods:The mRNA and protein levels of TBX1 in colorectal cancer cell lines HCT116, RKO, SW480, HT29, and LOVO were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Colorectal cancer cell lines HCT116 and SW480 cells with low TBX1 expression were transfected with either a pcDNA3.1 plasmid containing TBX1 mimics (TBX1 overexpression group) or an empty pcDNA3.1 plasmid (the control group). LOVO cells with high TBX1 expression were transfected with small interfering RNA (siRNA) targeting TBX1 including si-TBX1-8604A, si-TBX1-8604B, and a negative control siRNA (si-NC), which were treated as si-TBX1-8604A group, si-TBX1-8604B group, and si-NC group. qRT-PCR was used to detect the expressions of transcriptional level TBX1 and PARK2, and Western blot was used to detect the protein levels of TBX1, PARK2, and key factors in the MAPK and PI3K signaling pathways. Methyl Thiazolyl Tetrazolium (MTT) assay and cell colony formation assay were used to detect the cell proliferation. Combining literatures and the JASPAR database, 2 binding sites of TBX1 in the PARK2 promoter region were predicted. Chromatin immunoprecipitation assay was employed to verify the binding sites of TBX1 to PARK2 in HCT116 and SW480 cells. Dual luciferase reporter gene assay was used to verify the targeting relationship between TBX1 and PARK2. The expression of TBX1 and PARK2 in colon cancer tissues was analyzed by using the Cancer Genome Atlas (TCGA) database (September 2023).Results:High TBX1 expression in HCT116 and SW480 cells transfected with TBX1 mimics plasmid was confirmed by qRT-PCR and Western blot, while TBX1 expression was successfully knocked down in LOVO cells transfected with siRNA targeting TBX1. MTT assay indicated that the absorbance values for HCT116 cells in TBX1 overexpression group on d1, d3, d5, and d7 after inoculation, and for SW480 cells on d3, d5, and d7 after inoculation were lower than those in the control group, and the differences were statistically significant (all P < 0.01). LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group exhibited higher absorbance values than the si-NC group on d1, d3, d5, and d7 after inoculation, and the differences were statistically significant (all P < 0.05). Cell colony formation assay revealed that after 14 d, the colony number of HCT116 cells [(387±9) vs. (843±13)] and SW480 cells [(413±9) vs. (931±15)] in TBX1 overexpression group was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The colony number of LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group was (493±77) and (470±32), respectively, which was higher than that in the si-NC group (349±26), and the differences were statistically significant (all P < 0.05). The protein relative expression levels of p-ERK and p-AKT S473 in HCT116 and SW480 cells in TBX1 overexpression group were lower than those in the control group, while protein relative expression levels of p-ERK and p-AKT S473 in LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group were higher than those in the si-NC group, and the differences were statistically significant (all P < 0.05). The relative expression level of PARK2 mRNA in HCT116 and SW480 cells (all P < 0.01) and the protein level in the overexpression group were higher than those in the control group. Chromatin immunoprecipitation assay demonstrated that the enrichment times of TBX1 binding to 2 sites of PARK2 intron in HCT116 and SW480 cells in TBX1 overexpression group were higher than that in the control group, and the differences were statistically significant (all P < 0.05). Dual luciferase reporter gene assay showed that the relative luciferase activity of HCT116 and SW480 cells co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and pGL3 plasmid containing PARK2 mimics was higher than that of cells co-transfected with empty pcDNA3.1 and pGL3 plasmids, co-transfected with empty pcDNA3.1 plasmid and pGL3 plasmid containing PARK2 mimics, co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and empty pGL3 plasmid, and the differences were statistically significant (all P < 0.05). Spearman analysis showed that there was a positive correlation between transcriptional level TBX1 and PARK2 in colon cancer tissues (288 cases) in TCGA database ( r = 0.226, P < 0.001); and the relative expression level of PARK2 mRNA in colon cancer tissues (383 cases) was lower than that in normal intestinal tissues (50 cases), and the difference was statistically significant ( P < 0.001). Conclusions:Elevated expression of transcriptional factor TBX1 inhibits the proliferation of colorectal cancer cells, potentially by activating the downstream target gene PARK2 and inhibiting the phosphorylation of ERK and AKT in the MAPK and PI3K signaling pathways, ultimately affecting the activation of these pathways.

【Objective】 To evaluate and analyze the impact of COVID-19 epidemic on inventory of red blood cells (RBCs)in local and municipal blood stations in China, and to provide reference for the management of public health emergencies. 【Methods】 Relevant data from 2018 to 2021 were collected, and the differences in the volume of qualified RBCs, the usage efficiency of inventory RBCs, the average daily distribution of RBCs,the blood distribution rate of RBCs prepared by 400 mL whole blood, the difference in the average storage days of RBCs at the time of distribution, the average daily inventory of RBCs and the time of the average daily inventory of RBCs to maintain the distribution in 24 local and municipal blood stations in China during the COVID-19 epidemic and non-epidemic periods were retrospectively analyzed. 【Results】 Compared with non-epidemic periods, the volume of qualified RBCs [(117 525.979 ±52 203.175)U] and the average daily distribution of RBCs [( 156. 468 ± 70. 186) U ] increased significantly, but the usage efficiency of inventory RBCs decreased(97.24%±0.51%) significantly (P<0.05).There was no significant difference in the blood distribution rate of RBCs prepared by 400 mL whole blood(73.88%±20.30%), the average storage days of RBCs distribution(13.040 ±3.486), the average daily stock quantity of RBCs[(2 280.542 ±1 446.538) U ] and the time of the average daily inventory of RBCs to maintain the distribution[(15.062 ±7.453) d] (P>0.5). 【Conclusion】 During the COVID-19 epidemic, the inventory management of RBCs operated well, the overall inventory remained relatively stable, the stock composition and storage period showed no significant change.

AIM: To investigate the application of two-stage estimation (TSE) on adjustment for treatment switch in oncology trials. METHODS: The theory and implementation of TSE method was described, and was applied to adjust the data from a two-arm randomized controlled trial of anti-tumor drugs. The changes of survival curves and hazard ratio of two groups after adjustment for cross-over were evaluated. In addition, the results of two-stage estimation and rank preserving structural failure time model (RPSFT) were compared. RESULTS: After adjustment for cross-over using TSE methods, the results showed that the median survival time of control group was shorter than the original one, and the hazard ratio was lower than the observed value. Moreover, TSE method showed similar results to rank preserving structural failure time model. CONCLUSION: The TSE method is relatively simple to use, reliable and has a good practice property in cross-over analysis of oncology trials. At the same time, it is necessary to pay attention to its application scopes.

The Major of Medical Imaging Technology (Radiotherapy Technology Orientation) in West China Medical School, Sichuan University, has been devoted to training therapists, dosimetrists, and physicists in tumor radiotherapy, and it is urgently needed to improve the practice ability of interns and standardize the teaching system. In view of the current status of the practice of students in radiotherapy technology, this article analyzes and summarizes the teaching staff construction, teaching contents, teaching methods, and other aspects, finds out the problems and challenges in the current teaching system, and puts forward suggestions for practice teaching reform.

Objective To evaluate the feasibility of an in-room automated volumetric arc therapy (VMAT) planning engine based on dose volume histogram (DVH) prediction model in RayStation treatment planning system.Methods A total of 4,0 VMAT plans of cervix cancer,planned by experts,were chosen to build DVH estimation model by principal component regression analytic method.An in-room automated VMAT planning program based on IroPython scripting language combined with DVH prediction model was performed in RayStation treatment planning system.The DVH estimation model was applied to Another 10 testing cases of cervical cancer and the feasibility was evaluated by comparing the automatic plans with manual plans.Results The predicted DVH of organs at risk showed a good fit with real DVH in the ten testing cases.There were no statistically significant differences between manual and automatic plans in PTV conformal index (CI) and homogeneity index (HI) (P ＞ O.05).V40 and V50 of bladder were significantly decreased by 4.3％ and 1.6％ in automatic plans (t =2.75,5.26,P ＜ 0.05).V30,V40 and Vs0 of rectum were also decreased by 6.8％,5.8 ％ and 2.1％ (t =2.26,3.55,5.19,P ＜ 0.05).Both left and right femoral heads were better spared in automatic plans with average doses decreased by 380 and 322 cGy(t =5.55,7.25,P ＜ 0.05).The time of creating a treatment plan was 36 min for automatic plan and 53 min for manual plan.Conclusions The fully automated VMAT treatment plan program can create a VMAT plan of cervix cancer with high efficiency and good quality.

Objective To analyze the displacement of titanium clips for tumor bed localization after breast-conserving surgery for breast cancer and its influential factors.Methods A retrospective analysis was performed on the cone-beam computed tomography (CT) images of 14 patients with breast cancer who received radiotherapy after breast-conserving surgery from April to October,2016.The relative position of the chest wall and the errors of the titanium clips in radiotherapy were measured.A Pearson correlation analysis was used to analyze the correlation of the displacement of titanium clips with the relative position of titanium clips,the breast volume,the vertical distance between the titanium clips and the tangential line of the chest wall,and the maximum thickness of the breast.Results The system errors of the chest wall in left-right,superior-inferior,and anterior-posterior directions were 4.42,3.44,and 5.13 mm,respectively,and the random errors were 3.55,3.07,and 4.54 mm,respectively.The titanium clips had a large displacement relative to the chest wall,mainly in the left-right direction.The maximum system error was 4.39 mm and the random error was 2.42 mm.The displacement of titanium clips was not significantly correlated with the breast volume and the maximum thickness of the breast (P>0.05).However,the relative position of titanium clips in superior-inferior direction was significantly correlated with the displacement of the lowest,the most lateral,the most anterior,and the most posterior titanium clips (P<0.05).As to the uppermost clips,there was a significant difference in displacement between the clips close to the chest wall and the clips far from the chest wall (P=0.02).Conclusions Due to large setup error and displacement of titanium clips during radiotherapy,simultaneous integrated boost is not suitable for patients with breast cancer who are immobilized by vacuum cushion and received radiotherapy.The unstable immobilization may be the major influential factor for the displacement of titanium clips.

Objective To evaluate the efficacy and safety of short-term sensor-augmented insulin-pump (SAP) therapy for poorly controlled patients with type 1 diabetes mellitus (T1DM).Methods Sixty T1DM patients with glycosylated hemoglobin (HbA1c)>9.0% were randomly assigned to 2 groups treated with SAP or multiple daily insulin injection ( MDI) for 6 days, then all patients converted to MDI therapy. Results Compared with MDI group and before therapy, the mean blood glucose concentration ( MBG) , SD of blood glucose, mean amplitude of glycemic excursion ( MAGE) and 24-h area under curve at 10.0 ( AUC10.0 ) levels in SAP group significantly decreased after 6-day therapy ( compared with MDI group:t=1.761,P=0.028, t=2.569,P=0.037, t=2.712,P=0.020, t=2.985,P=0.014, compared with before therapy:t=3.128,P=0.006, t=2.689,P=0.024, t=2.966,P=0.013, t=3.076,P=0.009);while there was no difference in 24-h area under curve at 3.9 (AUC3.9) between groups (P>0.05).After 1 month follow-up HbA1c levels decreased in SAP group (t=2.344,P=0.023) and were significantly lower than those in MDI group (t=1.844, P=0.035).There was no difference in daily insulin dosage, fasting C peptide (FCP) and postprandial 2h C peptide (2hCP) between two groups (P>0.05).Age (t=2.125, P=0.012) and SAP therapy (t=3.376, P=0.009) were independently correlated with the HbA1c after 1 month.Conclusion Short-term SAP therapy is effective and safe for poorly controlled T1DM patients with rapid glucose lowering and glycemic excursions reduction.

A total of 473 patients of diabetic nephropathy (DN) with normal serum creatinine were recruited.Blood routine,blood lipids and urine albumin/creatinine ratio (UACR) were measured.They were divided into microalbuminuria group (DN1,n =246 ) and macroalbuminuria group (DN2,n =227 ).The white blood cell (WBC) count,monocyte count and CRP significantly increased with the progression of DN in the DN2 group versus those in the DNI group [ (6.8 ± 1.7 ) × 109/L vs.(6.3 ± 1.5 ) × 109/L,(0.49±0.23) ×109/Lvs.(0.32 ±0.21) ×109/L,(4.1 ±1.1)mg/Lvs.(1.7±0.3) mg/L,all P＜ 0.05].According to multiple linear regression analysis,WBC,monocyte,low density lipoproteincholesterol and lymphocyte were found to be independent influencing factors for the elevation of UACR.

Objective To study the impairment and the expression of receptor of advanced glycation endproduct (RAGE) in cultured rat glomerular mesangial cells ( GMC ) induced by constant and intermittent high glucose, and to investigate the pathogenesis of diabetic nephropathy. Methods After being cultured under constant and intermittent high glucose with different concentrations for 24 and 48 hours, the morphological changes of rat mesangial cells were observed, the proliferation of GMC was detected by MTT assay, the activity of superoxide dismutase (SOD)and the level of malondialdehyde (MDA)in supernatant were measured by spectrophotometer,and the expressions of RAGE mRNA were evaluated by RT-PCR. Results ( 1 ) Compared with the control group,the cellular morphology was changed in case of constant and intermittent high glucose. The damage of GMC with intermittent high glucose concentrations was more serious. (2)The activity of SOD was decreased and the level of MDA was raised in case of intermittent high glucose concentrations compared with the constant high glucose concentrations (P＜0.05). (3)The expression of RAGE mRNA with intermittent high glucose concentrations was significantly higher than that with constant high glucose concentrations ( P＜0. 01 ). Conclusions The damaging effects and increased expression of RAGE in cultured rat GMC induced by blood glucose fluctuation was much worse than that with constant high glucose. The blood glucose fluctuation may be one of the causes that induce diabetic nephropathy.

Objective To investigate the relationship between serum transforming growth factor- β1(TGF- β1) levels and early diabetic nephropathy and clarify whether valsartan plays a role in renal protection by reducing the level of serum TGF-β1. Methods The study subjects were divided into four groups:control group (30 cases); normal albuminuria group 1 (NA1 group with 12 cases, U MA/Cr < 10 μg/mg combined with type 2 diabetes);normal albuminuria group 2 (NA2 group with 19 cases,UMA/Cr 10-30 μg/mg combined with type 2 diabetes); microalbuminuria group ( MA group with 35 cases, U MA/Cr 31-300 μg/mg combined with type 2 diabetes). All these type 2 diabetic patients were suffering from diabetic retinopathy, and valsartan ( 80 mg/d) were medicated for those combined with hypertension. The serum TGF-β1 levels were measured by enzyme-linked immunosorbent assay in all subjects. Results Serum TGF- β1 levels in three diabetes groups were (7.41 ± 2.68 ), ( 10.52 ± 4.10), (22.98 ± 43.74) ng/L, respectively, all of which were higher than those in control group [(4.25 ± 5.82) ng/L] (P < 0.05). There were significant differences in serum TGF- β1 levels among MA group, NA2 group and NA1 group (P < 0.05 ). Serum TGF-β1 levels in NA1 group with valsartan treatment significantly decreased compared with those without valsartan treatment (P < 0.05), whereas there was no significant reduction in NA2 and MA group with valsartan treatment (P > 0.05). Conclusions High serum TGF-β1 level may be associated with type 2 diabetes and early diabetic nephropathy. Early intervention of valsartan may be delay the onset and development of diabetic nephropathy by decreasing the serum TGF-β1 level.