OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

Objective:To explore the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and readmission in patients with chronic aplastic anemia (AA).Methods:A total of 105 patients with chronic AA who were hospitalized at the Fuyang People′s Hospital Affiliated to Anhui Medical University from January 2020 to December 2022 were selected. The serum 25(OH)D level was measured using chemiluminescence method, and it was divided into low value group and high value group based on the average value. We compared the clinical data differences between two groups of patients, used logistic multivariate analysis to identify the risk factors for readmission in chronic AA patients, and used the Kaplan Meier method to plot curves to compare the differences in readmission rates and readmission intervals between the two groups.Results:The difference in the interval between readmission between patients in the low value group (<19.39 ng/ml) and those in the high value group (≥19.39 ng/ml) was statistically significant [(2.61±1.03)months vs (3.27±1.32)months, P<0.05]. A higher level of serum 25(OH)D was a protective factor in reducing the risk of readmission ( OR: 0.739; 95% CI: 0.569-0.962) and prolonging the interval between readmission (Log Rank=0.004, Breslow=0.01, Tarone-Ware=0.005; P<0.05) in chronic patients, while long course of illness was a risk factor for readmission ( OR=3.432, P=0.006). Patients in the low value group who had accumulated the use of vitamin D supplements for ≥3 weeks had a significantly longer interval between readmission ( P<0.001). Conclusions:Abnormal reduction of serum 25(OH)D levels can shorten the interval between readmission and increase the risk of readmission in chronic AA patients.

Objective:To investigate the effect of the combination of rituximab injection and cyclophosphamide+ hydroxydoxorubicin+ oncovin+ prednisone (CHOP) regimen on serum lactate dehydrogenase (LDH) and β 2-microglobulin (β 2-MG) levels in patients with non Hodgkin′s lymphoma (NHL).Methods:A total of 92 NHL patients admitted to the Hematology Department of Fuyang People′s Hospital from January 2020 to May 2023 were selected and randomly divided into an observation group ( n=46) and a control group ( n=46) using a random number table method. The control group received chemotherapy intervention with CHOP regimen; The observation group received intravenous infusion of rituximab injection 1 day before the start of CHOP chemotherapy. After 6 consecutive cycles of treatment (1 cycle for 21 days), the efficacy and adverse reactions, the levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], T lymphocytes [surface antigen differentiation cluster 4 (CD4 + ), surface antigen differentiation cluster 8 (CD8 + ), CD4/CD8, helper T cells 17 (Th17)], vascular endothelial growth factor (VEGF), LDH, and β2-MG of the two groups were compared after treatment. Results:The total remission rate of the observation group was 80.43%(37/46), which was higher than that of the control group, which was 60.87%(28/46), and the difference was statistically significant ( P<0.05). Compared with before treatment, TNF-α and IL-6 levels decreased, Th17 and CD8 + levels increased in both groups after treatment, and the difference was statistically significant (all P<0.05); After treatment, the TNF-α and IL-6 levels in the observation group were lower than those in the control group, and Th17 levels were higher than those in the control group, with statistically significant differences (all P<0.05). Compared with before treatment, the LDH, β2-MG, and VEGF levels in the two groups decreased significantly after treatment (all P<0.05); After treatment, the LDH, β2-MG, and VEGF levels in the observation group were lower than those in the control group, and the differences were statistically significant (all P<0.05). The total incidence rates of adverse reactions in the two groups were 86.96%(40/46) and 80.43%(37/46), respectively, with no statistically significant difference ( P>0.05). Conclusions:The combination of rituximab injection and CHOP regimen for NHL treatment can effectively alleviate inflammation, improve LDH, β 2-MG, VEGF levels, and enhance efficacy. The safety is similar to using CHOP regimen alone, and it is worth promoting and applying.

Objective:To investigate the potential value of saccade and antisaccade parameters in early identification of Parkinson′s disease (PD) and its motor subtypes.Methods:A total of 111 PD patients [tremor dominant (TD) type in 45, postural instability/gait difficulty (PIGD) type in 54 and indeterminate type in 12)] and 54 healthy controls were recruited from Department of Neurology, Guangdong Provincial People′s Hospital from July 2022 to July 2023. All subjects underwent oculomotor test including visually guided saccades and volitional antisaccades by the Eyeknow-M10-B Eye tracker. For PD patients, TD and PIGD scores were measured using the Movement Disorder Society Unified Parkinson′s Disease Rating Scale (MDS-UPDRS) Part Ⅱ and Part Ⅲ. Oculomotor parameters among TD, PIGD patients and healthy controls were firstly compared. Multiple linear regression analyses were performed to assess the relationship between ocular parameters with differences and TD/PIGD score. Then receiver operating characteristic (ROC) curve analysis was made between PD patients and healthy controls, as well as between PIGD and TD subtypes.Results:Compared to healthy controls, PD patients showed significantly decreased saccadic accuracy [100.0%(90.0%, 100.0%) vs 100.0%(100.0%, 100.0%), U=1 732.500, P<0.001], prolonged latency [252.2(228.5, 300.1) ms vs 227.7(214.2, 241.8) ms, U=1 401.000, P<0.001], minimum duration [233.6(211.2, 278.8) ms vs 211.0(200.0, 222.5) ms, U=1 534.500, P<0.001], average duration [356.6(313.8, 427.8) ms vs 279.4(267.4, 312.9) ms, U=881.000, P<0.001],as well as decreased peak [444.4(335.0, 593.7) °/s vs 526.7(412.6, 696.2) °/s, U=1 971.000, P=0.007] and average velocity [196.3(144.4, 240.5) °/s vs 256.7(226.7, 312.0) °/s, U=1 330.000, P<0.001] in saccades. And in antisaccades, PD patients also showed prolonged latency [432.0(362.9, 599.8) ms vs 352.9(309.8, 407.6) ms, U=1 553.000, P<0.001], minimum duration [333.4(299.8, 377.6) ms vs 290.1(263.9, 332.9) ms, U=1 608.000, P<0.001], average duration [518.2(462.7, 603.5) ms vs 424.2(377.1, 473.5) ms, U=1 181.000, P<0.001], decreased peak [458.5(327.9, 604.3) °/s vs 560.4(440.3, 698.5) °/s, U=1 838.500, P=0.001] and average velocity [186.6(143.1, 228.1) °/s vs 263.2(217.2, 301.5) °/s, U=1 131.000, P<0.001]. There was no statistically significant difference in antisaccadic accuracy [55.0%(15.0%, 80.0%) vs 66.7%(39.4%, 86.9%), U=2 167.500, P=0.053]. Compared with TD subtype, PIGD patients showed significantly decreased antisaccadic peak velocity [416.2(300.3, 534.3) °/s vs 527.1(402.3, 636.4) °/s, U=-26.474, P=0.009]. After adjusting for age, gender and education, antisaccadic peak velocity was negatively correlated with PIGD score in PD patients (β=-0.296, P=0.001), and no correlation with TD score was found. The ROC analysis was performed on combined saccadic and antisaccade metrics between PD patients and healthy controls, with area under the curve (AUC) as 0.918. For antisaccadic peak velocity between PIGD and TD subtypes, the AUC was 0.690. Conclusions:Eye movement metrics have potential value in distinguishing PD patients from healthy controls. The antisaccadic peak velocity is related to the severity of motor symptoms in PIGD patients, which is helpful for distinguishing the motor subtypes of PD patients.

Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.

Transuranics radionuclides are ubiquitous in the environment. Long term intake will cause internal radiation hazards, and it is also an important source of radioactive contamination to the environment in the future. In this paper, the source and migration behavior of transuranic radionuclides are reviewed, the existing problems in China are summarized, and the suggestions for future work are put forward.

Objective:To investigate the influencing factors for endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events in novice trainees and establishment of its prediction model.Methods:The prospective study was conducted. The clinical data of 12 novice trainees of ERCP in the First Hospital of Lanzhou University from July 2016 to July 2019 were selected. The operation was performed by 12 novice trainees of ERCP under the guidance of the endoscopic experts. Observation indicators: (1) ERCP-related adverse events in novice trainees; (2) analysis of influencing factors for ERCP-related adverse events in novice trainees; (3) establishment of a prediction model for ERCP-related adverse events in novice trainees. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M(range), and com-parison between groups was analyzed by the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. The Logistic regression model was used for univariate and multivariate analyses. The regression coefficients were used to construct a prediction model. The receiver operating characteristic curve was drawn, and the area under curve was used to evaluate the predictive ability. Results:(1) ERCP-related adverse events in novice trainees. Of the 300 patients with ERCP operated by 12 novice trainees, 52 cases had ERCP-related adverse events and 248 cases had no ERCP-related adverse events. Cases in grade 1?2 or grade 3?4 of ERCP difficulty classification, score for intubation time, score for cannulation time, cases with or without completion of the cannulation, cases with or with-out basket stone removal, cases with or without stenosis expansion, score for contrast-enhanced interpretation, score for implementation of reasonable treatment and score for expected purpose reached were 22, 30, 8(range, 5?10), 20(rang, 9?20), 24, 28, 11, 41, 0, 52, 39±17, 39±19 and 44±23 for novice trainees with ERCP-related adverse events, versus 146, 102, 6(range, 4?9), 12(range, 8?20), 163, 85, 94, 154, 20, 228, 52±22, 80±20, 52±23 for novice trainees without ERCP-related adverse events, showing significant differences in the above indicators between them ( χ2=4.79, Z=?2.46, ?2.72, χ2=7.01, 5.30, 4.49, t=?4.00, ?2.97, ?2.29, P<0.05). (2) Analysis of influencing factors for ERCP-related adverse events in novice trainees. Results of univariate analysis showed that the diffi-culty classification of ERCP, intubation time, cannulation time, completion of cannulation, basket stone extraction, contrast-enhanced interpretation, implementation of reasonable treatment and expected purpose reached were related factors for ERCP-related adverse events in novice trainees ( odds ratio=1.95, 1.11, 1.08, 0.45, 0.44, 0.97, 0.98, 0.98, 95% confidence intervals as 1.07?3.58, 1.02?1.22, 1.02?1.14, 0.24?0.82, 0.22?0.90, 0.96?0.99, 0.96?0.99, 0.97?1.00, P<0.05). Results of multi-variate analysis showed that difficulty classification of ERCP and contrast-enhanced interpretation were independent influencing factors for ERCP-related adverse events in novice trainees ( odds ratio=2.08, 0.95, 95% confidence intervals as 1.10?3.96, 0.92?0.99, P<0.05). (3) Establishment of a predic-tion model for ERCP-related adverse events in novice trainees. According to the important outcome indicators of clinical training and results of multivariate analysis, 4 indicators including difficulty classification of ERCP, intubation time, cannulation time and contrast-enhanced interpretation were included to establish a prediction model for ERCP-related adverse events in novice trainees, which indicated that trainees with the predicted score >0.4 were in high risk of ERCP-related adverse events. The area under receiver operating characteristic curve of the prediction model was 0.72(95% confidence interval as 0.65?0.79, P<0.05), with the best cut-off value as 0.40, the sensitivity as 76.9% and the specificity as 63.3%. Conclusion:The difficulty classification of ERCP and contrast-enhanced interpretation are independent influencing factors for ERCP-related adverse events in novice trainees. Novice trainees with a predicted score >0.4 are high-risk groups of ERCP-related adverse events.

Objective:To explore the application of "upgraded single-entry colonoscope training method" in the primary endoscopic training of refresher doctors.Methods:A total of 71 refresher doctors who participated in the primary single endoscopy training in the Endoscopy Center of the Affiliated Hospital of Qingdao University from January 2017 to December 2019 were randomized to two groups: upgraded single-entry endoscopy training group ( n=36) and traditional single-entry endoscopy training group ( n=35). In the first week of training, all the participants learned the basic theory of single-entry enteroscopy insertion. From week 2 to week 11, each doctors of the two groups finally completed 80 to 100 cases of single-entry endoscopy. The upgraded single-entry colonoscopy training group was divided into two stages: "rectum-proximal sigmoid colon" and "descending colon-ileocecal part" with the boundary of descending-sigmoid colon as the dividing point, which was different from the traditional group. At the 12th week, each doctors were assessed by 20 cases of single-entry colonoscopy operation. the success rate of ileocecum insertion, the time to pass through sigmoid colon, the rate of loop formation and the average operation time of successful ileocecum insertion were compared between the two groups. SPSS 26.0 was used for t test or chi-square test. Results:Compared with the traditional single-entry endoscopy training group, the upgraded single-entry endoscopy training group achieved better results in the successful rate of ileocecal insertion (66.8% vs. 59.0%, P=0.005), the time to pass sigmoid colon [(6.05±3.32) min vs. (7.15±3.12) min, P<0.001], the loop rate (35.13% vs. 40.71%, P=0.035), the average operation time of successfully inserting the ileocecal part [(9.01±2.12) min vs. (10.25±3.12) min, P<0.001] and the discomfort response score [(5.19±1.41) vs. (6.70±2.15), P<0.001], with statistical significance between the groups. Conclusion:"Upgraded single-entry endoscopy training method" emphasizes no loop through sigmoid colon, which is more helpful for refresher doctors to master the operation skills of single-entry colonoscopy, shorten the teaching time, and reduce the discomfort of patients, and is suitable for popularization in the teaching.

Objective:To investigate the differences in clinical features and imaging findings of cirrhotic patients with fundic varices between gastroesophageal varices type 2 (GOV2) and isolated fundic varices type 1 (IGV1).Methods:Clinical and imaging data of cirrhotic patients with fundic varices treated in Union Hospital, Tonji Medical Colloge, of Huazhong University of Science and Technology from October 2013 to March 2021 were retrospectively analyzed.Results:A total of 210 patients were enrolled, including 139 patients of GOV2 (GOV2 group) and 71 patients of IGV1 (IGV1 group). Blood routine examination results showed that the median value of hemoglobin in GOV2 group was lower than that in IGV1 group(91.00 g/L VS 112.00 g/L, P<0.05). The incidence of portal hypertensive gastropathy (PHG) in GOV2 group was higher than that in IGV1 group [20.14% (28/139) VS 5.63% (4/71), P<0.05]. The incidence of peptic ulcer was lower in GOV2 group than that in IGV1 group [12.23% (17/139) VS 38.03% (27/71), P<0.05]. The median diameter of portal veins in GOV2 group was larger than that in IGV1 group (15.09 mm VS 12.85 mm, P<0.05), and the volume of gastric fundus varices in GOV2 group was smaller than that in IGV1 group (2.14 mL VS 10.00 mL, P<0.05). The proportion of afferent veins in left gastric vein in GOV2 group was higher than that in IGV1 group [98.43% (125/127) VS 77.78% (42/54), P<0.05], and the median diameter of left gastric vein in GOV2 group was larger than that in IGV1 group (5.58 mm VS 4.53 mm, P<0.05). The efferent vessels mainly included gastrorenal shunt and splenorenal shunt. The incidences of gastrorenal shunt [27.56% (35/127) VS 66.67% (36/54)] and splenirenal shunt [12.60% (16/127) VS 25.93% (14/54)] in GOV2 group were lower than those in IGV1 group ( both P<0.05). The incidences of venae parumbilicales vein [38.58% (49/127) VS 12.96% (7/54)] and retroperitoneal collateral shunt [30.71% (39/127) VS 11.11% (6/54)] in GOV2 group were higher than those in IGV1 group (both P<0.05). Conclusion:There is significant heterogeneity in clinical features and imaging findings between cirrhotic patients complicated with GOV2 and IGV1. Recognizing and understanding the differences between the two types of patients is beneficial to taking appropriate clinical measures and improving patient prognosis.

Objective:To overcome the disadvantages of bismuth removal by bismuth sulfide precipitation method recommended by existing analytical standards and improve the quality of analytical result.Methods:Based on 201×7 anion exchange resin, the experimental process of bismuth removal was designed, and verified by using spiked samples and IAEA test samples.Results:Bismuth was removed by anion exchange resin. In the removal experiments of strontium, yttrium and bismuth, the chemical recovery rate of strontium and yttrium could reach (98.6 ± 0.8)% and (98.5 ± 0.7)%, respectively, with no Bi 2S 3 precipitation found. The relative standard deviation between analytical result and theoretical values was -2.97% to 5.94%, better than 3.96%-17.8% by the standard bismuth removal method. Through validation using IAEA test samples, the relative standard deviation between the reported value and the target value for 90Sr was between 3.40%-7.09%, and all the results were acceptable. Conclusions:Bismuth could be quantitatively removed using anion exchange resin without adsorption of strontium and yttrium. In addition, the bismuth removal solution system of anion exchange resin was the same as the elution system in 90Sr analysis, and the purpose of rapid bismuth removal could be achieved without conversion system. Compared with the current standard analytical method, it was feasible and better to quantitatively remove bismuth based on anion exchange resin, which could meet the needs of routine analysis of 90Sr.