Objective:To assess intrafractional errors of the deformation of clinical target volumes (CTVs) during online adaptive radiotherapy (OART) for prostate cancer patients, aiming to provide a basis for online plan optimization.Methods:A retrospective analysis was conducted for 13 prostate cancer patients who received 1.5 T magnetic resonance imaging (MRI)-guided OART (8 Gy × 5 fractions, totaling 65 fractions) at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences. The MRI images were collected at the beginning and end of various treatment fractions. Then, the CTVs and organs at risk (OARs) were delineated by the same radiation oncologist. After rigid registration and triangle mesh generation, the surface vertices were extracted. The deformable registration for the CTV surfaces was performed using the thin-plate spline robust point matching (TPS-RPM) algorithm, yielding vertex correspondences. Last, both systematic and random intrafractional errors of CTV deformation were calculated.Results:The average Hausdorff distance (HD) for deformable registration of treatment fractions was (1.68 ± 0.28) mm. The intrafractional systematic errors of CTV deformation were (0.25 ± 3.18) mm (anterior-posterior direction; A-P), (0.89 ± 3.85) mm (left-right direction, L-R), and (-1.98 ± 6.69) mm (superior-inferior direction, S-I). The intrafractional random errors of CTV deformation were determined at (-0.26 ± 1.89) mm (A-P), (-0.08 ± 0.88) mm (L-R), and (-0.04 ± 1.86) mm (S-I).Conclusions:During OART, CTV deformations primarily occur in the S-I direction. Therefore, it is necessary to consider the expanded size of margins in this direction during OART for prostate cancer.

Objective : To analyze the relationship between tongue volume, tongue position, dental and skeletal parameters in adult patients with different skeletal malocclusions, providing references for the etiology, diagnosis, and treatment of skeletal malocclusions. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Cone-beam computed tomography (CBCT) and cephalometric radiographs were collected from 60 adult patients, divided into three groups based on ANB angle values: skeletal Class I (0° < ANB < 4°), II (ANB > 4°), and III (ANB < 0°), with 20 cases in each group. Dental and skeletal parameters were measured using Dolphin software. Mimics software was used for 3D reconstruction of the tongue, oral cavity, and upper airway to measure tongue position, tongue volume, oral cavity volume, and upper airway volume, followed by statistical analysis. Results: The skeletal Class III group had significantly larger tongue and oral cavity volumes than the skeletal Class I and Class II groups (P = 0.02). Tongue length in the skeletal Class III group was also greater than in the skeletal Class I and Class II groups (P = 0.016). There was no significant difference in the ratio of tongue volume/oral cavity capacity among the three skeletal malocclusion groups (P > 0.05). Tongue volume was positively correlated with U1-SN and negatively correlated with overbite and overjet (P < 0.05). Additionally, tongue volume showed a significant positive correlation with Go-Gn and Pg-Np (P < 0.01), as well as with maxillary and mandibular dental arch width and basal bone arch width (P < 0.01). Upper airway volume was positively correlated with TT-VRL and TP-VRL (P < 0.05). Conclusion Patients with skeletal Class III malocclusion have larger tongue volumes and longer tongues. Patients with larger tongue volumes may also have larger, more forward-positioned mandibles. Patients with more posterior tongue positions may have smaller upper airway volumes. When developing orthodontic or orthognathic treatment plans, it is crucial to consider the relationship between tongue position, tongue volume, the jaws, and the airway to ensure optimal outcomes for both dental and orofacial function.

BACKGROUND:Physiotherapy is very important for the recovery after anterior cruciate ligament reconstruction.In recent years,many doctors are optimizing the physical rehabilitation program after anterior cruciate ligament reconstruction.However,there is still a lack of efficient rehabilitation training after anterior cruciate ligament reconstruction. OBJECTIVE:To investigate the effect of vibration therapy combined with suspension training on movement and knee joint function after anterior cruciate ligament reconstruction. METHODS:A total of 80 patients undergoing first unilateral anterior cruciate ligament reconstruction at the Affiliated Sport Hospital,Shanghai University of Sport were randomly divided into vibration therapy group(n=40)and vibration therapy+suspension training group(n=40).In the vibration therapy group,vibration therapy(10 minutes each,once a day,6 times per week)was performed at the 13th week after anterior cruciate ligament reconstruction.Patients in the vibration therapy+suspension training group were treated with vibration therapy(10 minutes each,once a day,6 times per week)and suspension training(twice a week)at the 13th week after anterior cruciate ligament reconstruction.Training in each group was performed for 8 weeks.Knee joint function was evaluated by knee joint Lysholm score before and 8 weeks after training.The symmetry index was evaluated by the isokinetic muscle strength evaluation training system.The balance test system was used to evaluate the average trace error difference of the bilateral multi-axes. RESULTS AND CONCLUSION:Compared with those before training,the knee Lysholm score and the knee extension and flexion symmetry indexes increased(P<0.05),and the average trace error difference decreased after training(P<0.05).Compared with the vibration therapy group,the knee Lysholm score in the vibration therapy+suspension training group increased(P<0.05),the knee extension and knee flexion symmetry index increased(P<0.05),and the average trace error difference decreased(P<0.05).To conclude,compared with vibration therapy training alone,vibration therapy combined with suspension training can significantly improve knee joint function,increase muscle strength and symmetry,and improve balance stability in patients undergoing anterior cruciate ligament reconstruction.

To assess the implantation effectiveness of porous scaffolds, it is essential to consider not only their mechanical properties but also their biological performance. Given the high cost, long duration and low reproducibility of biological experiments, simulation studies as a virtual alternative, have become a widely adopted and efficient evaluation method. In this study, based on the secondary development environment of finite element analysis software, the strain energy density growth criterion for bone tissue was introduced to simulate and analyze the cell proliferation-promoting effects of four different lattice porous scaffolds under cyclic compressive loading. The biological performance of these scaffolds was evaluated accordingly. The computational results indicated that in the early stages of bone growth, the differences in bone tissue formation among the scaffold groups were not significant. However, as bone growth progressed, the scaffold with a porosity of 70% and a pore size of 900 μm demonstrated markedly superior bone formation compared to other porosity groups and pore size groups. These results suggested that the scaffold with a porosity of 70% and a pore size of 900 μm was most conducive to bone tissue growth and could be regarded as the optimal structural parameter for bone repair scaffold. In conclusion, this study used a visualized simulation approach to pre-evaluate the osteogenic potential of porous scaffolds, aiming to provide reliable data support for the optimized design and clinical application of implantable scaffolds.
Tissue Scaffolds/chemistry* ; Porosity ; Finite Element Analysis ; Tissue Engineering/methods* ; Computer Simulation ; Bone Development ; Osteogenesis ; Humans ; Cell Proliferation

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective:To explore the correlation between hyperuricemia (HUA) and chronic kidney disease (CKD) in the individuals undergoing physical examinations.Methods:It was a retrospective cohort study. The study selected 6 910 individuals who received health check-ups at the Xiangya Hospital Health Management Center of Central South University in 2012 and 2022, with none of them having developed CKD in 2012. Using the presence of HUA in 2012 as the independent variable and the occurrence of CKD in 2022 as the outcome variable, four Cox proportional hazards regression models were constructed, with baseline age, gender, body mass index, waist circumference, glomerular filtration rate, presence of hypertension, presence of diabetes, presence of dyslipidemia, white blood cell count, hemoglobin level, direct bilirubin level, alanine aminotransferase level, and blood uric acid level in 2013 as confounding variables. These models were used to analyze the correlation between HUA and CKD, and sensitivity analyses were conducted. The percentile bootstrap method was employed to conduct mediation effect testing, analyzing the intermediary risk factors that influence the correlation between HUA and CKD.Results:Among the 6 910 participants included in the study, the overall baseline detection rate of HUA was 8.78% (607/6 910). In 2022, the incidence of CKD was 7.2% (498/6 910). Cox regression analysis showed a positive correlation between HUA and the occurrence of CKD in the overall population ( HR=1.586, 95% CI: 1.224-2.055). However, after gradually adjusting for confounding factors, the correlation between HUA and CKD was not statistically significant. Stratified by gender, the occurrence of HUA was positively correlated with the incidence of CKD in women ( HR=2.599, 95% CI: 1.069-6.316), but the correlation became non-significant after adjusting for confounding factors. In contrast, there was no significant correlation between HUA and CKD in men. In sensitivity analysis, When uric acid levels were analyzed by grouping participants into two categories based on thresholds of>420 μmol/L for men and>360 μmol/L for women, or as a continuous variable, the results showed a positive correlation between HUA and CKD in the overall population and in women, the HR (95% CI) value was 1.627 (1.282-2.064), 2.465 (1.552-3.914), 1.004 (1.003-1.005) and 1.006 (1.004-1.008), respectively. However, after adjusting for confounding factors, the correlation between HUA and CKD became non-significant in both cases. In the males, there was no correlation between uric acid and the occurrence of CKD, regardless of whether uric acid was treated as a categorical or continuous variable. Mediation analysis revealed that diabetes and hypertension were full mediators between HUA/blood uric acid levels and CKD in the overall population. Among males, diabetes and hypertension were full mediators between blood uric acid levels and CKD. In females, hypertension was a full mediator between HUA/blood uric acid levels and CKD, with an effect proportion of 100%. Conclusion:HUA is positively correlated with the risk of CKD, particularly in females, but HUA is not an independent predictor of CKD. HUA influences the occurrence of CKD through conditions such as diabetes and hypertension.

Objective:To assess intrafractional errors of the deformation of clinical target volumes (CTVs) during online adaptive radiotherapy (OART) for prostate cancer patients, aiming to provide a basis for online plan optimization.Methods:A retrospective analysis was conducted for 13 prostate cancer patients who received 1.5 T magnetic resonance imaging (MRI)-guided OART (8 Gy × 5 fractions, totaling 65 fractions) at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences. The MRI images were collected at the beginning and end of various treatment fractions. Then, the CTVs and organs at risk (OARs) were delineated by the same radiation oncologist. After rigid registration and triangle mesh generation, the surface vertices were extracted. The deformable registration for the CTV surfaces was performed using the thin-plate spline robust point matching (TPS-RPM) algorithm, yielding vertex correspondences. Last, both systematic and random intrafractional errors of CTV deformation were calculated.Results:The average Hausdorff distance (HD) for deformable registration of treatment fractions was (1.68 ± 0.28) mm. The intrafractional systematic errors of CTV deformation were (0.25 ± 3.18) mm (anterior-posterior direction; A-P), (0.89 ± 3.85) mm (left-right direction, L-R), and (-1.98 ± 6.69) mm (superior-inferior direction, S-I). The intrafractional random errors of CTV deformation were determined at (-0.26 ± 1.89) mm (A-P), (-0.08 ± 0.88) mm (L-R), and (-0.04 ± 1.86) mm (S-I).Conclusions:During OART, CTV deformations primarily occur in the S-I direction. Therefore, it is necessary to consider the expanded size of margins in this direction during OART for prostate cancer.

Objective:To explore the correlation between hyperuricemia (HUA) and chronic kidney disease (CKD) in the individuals undergoing physical examinations.Methods:It was a retrospective cohort study. The study selected 6 910 individuals who received health check-ups at the Xiangya Hospital Health Management Center of Central South University in 2012 and 2022, with none of them having developed CKD in 2012. Using the presence of HUA in 2012 as the independent variable and the occurrence of CKD in 2022 as the outcome variable, four Cox proportional hazards regression models were constructed, with baseline age, gender, body mass index, waist circumference, glomerular filtration rate, presence of hypertension, presence of diabetes, presence of dyslipidemia, white blood cell count, hemoglobin level, direct bilirubin level, alanine aminotransferase level, and blood uric acid level in 2013 as confounding variables. These models were used to analyze the correlation between HUA and CKD, and sensitivity analyses were conducted. The percentile bootstrap method was employed to conduct mediation effect testing, analyzing the intermediary risk factors that influence the correlation between HUA and CKD.Results:Among the 6 910 participants included in the study, the overall baseline detection rate of HUA was 8.78% (607/6 910). In 2022, the incidence of CKD was 7.2% (498/6 910). Cox regression analysis showed a positive correlation between HUA and the occurrence of CKD in the overall population ( HR=1.586, 95% CI: 1.224-2.055). However, after gradually adjusting for confounding factors, the correlation between HUA and CKD was not statistically significant. Stratified by gender, the occurrence of HUA was positively correlated with the incidence of CKD in women ( HR=2.599, 95% CI: 1.069-6.316), but the correlation became non-significant after adjusting for confounding factors. In contrast, there was no significant correlation between HUA and CKD in men. In sensitivity analysis, When uric acid levels were analyzed by grouping participants into two categories based on thresholds of>420 μmol/L for men and>360 μmol/L for women, or as a continuous variable, the results showed a positive correlation between HUA and CKD in the overall population and in women, the HR (95% CI) value was 1.627 (1.282-2.064), 2.465 (1.552-3.914), 1.004 (1.003-1.005) and 1.006 (1.004-1.008), respectively. However, after adjusting for confounding factors, the correlation between HUA and CKD became non-significant in both cases. In the males, there was no correlation between uric acid and the occurrence of CKD, regardless of whether uric acid was treated as a categorical or continuous variable. Mediation analysis revealed that diabetes and hypertension were full mediators between HUA/blood uric acid levels and CKD in the overall population. Among males, diabetes and hypertension were full mediators between blood uric acid levels and CKD. In females, hypertension was a full mediator between HUA/blood uric acid levels and CKD, with an effect proportion of 100%. Conclusion:HUA is positively correlated with the risk of CKD, particularly in females, but HUA is not an independent predictor of CKD. HUA influences the occurrence of CKD through conditions such as diabetes and hypertension.

Objective To analyze the postmarketing safety characteristics of three immunomodulatory drugs(IMiDs)(thalidomide,lenalidomide and pomalidomide)in order to provide reference for clinical rational drug use.Methods The Open Vigil 2.0 tool was used to collect adverse drug event(ADE)reporting data from the U.S.Food and Drug Administration's(FDA)Adverse Event Reporting System(FAERS)between the first quarter of 2013 and the second quarter of 2022 for three IMiDs as primary suspect drugs.High frequency ADE was analyzed by mapping according to Medical Dictionary for Regulatory Activities(MedDRA terminology)25.0.The effective signals of adverse drug reactions(ADR)were screened according to the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods,and the high-intensity signals were analyzed.Results Among the top 20 ADEs,peripheral neuropathy,decreased blood count,thrombosis,skin squamous cell carcinoma and other ADEs occurred in all three drugs,but the distribution of the involved tissues and organs was different.Among the top 20 ADR signals,nearly half of the ADR signals of the 3 drugs were also in the high-frequency ADE range,among which 3 drugs showed increased human chorionic gonadotrophin,thalidomide and lenalidomide showed false positives in pregnancy tests,rectal adenocarcinoma and colorectal adenocarcinoma,and pomalidomide and lenalidomide showed decreased complete blood counts.Conclusion The overall ADE distribution of the three diamines is consistent,but there are some differences in the specific ADR signal characteristics.In clinical application,more attention should be paid to hemocytopenia,peripheral neuropathy,thrombus and second primary malignant tumors.