Transthyretin cardiac amyloidosis (ATTR-CA) is a restrictive cardiomyopathy caused by the abnormal deposition of transthyretin (TTR) in the myocardial interstitium, which often manifests as heart failure, atrial fibrillation, and conduction disorders. The significant heterogeneity of its clinical presentation poses a major challenge to accurate diagnosis. The dissociation of the TTR tetramer is the key initiating step of amyloid deposition in ATTR-CA, but the TTR tetramer is not currently included among the clinically applied biomarkers. This article systematically reviews the conventional biomarkers for ATTR-CA and focuses on discussing the potential value of the TTR tetramer as a novel indicator. Investigating the concentration, peak profile, and dissociation rate of the TTR tetramer is of great value for achieving early identification, risk stratification, and prognostic judgment of ATTR-CA.

Objective:Papillary thyroid carcinoma with a maximum tumor diameter of ≤1 cm was defined as papillary thyroid carcinoma (PTC). To explore the clinical risk factors of central lymph node metastasis (CLNM) in PTC at different locations.Methods:The clinical and pathological data of 1383 cases with solitary PTC in Hangzhou First People’s Hospital were retrospectively analyzed, and they were divided into isthmus group (175 cases), near-isthmus group (95 cases) and lateral lobe group (1113 cases) according to their tumor location. Univariate and multivariate analyses were used to analyze the relationship between gender, age, tumor maximum diameter, Hashimoto’s thyroiditis (HT) and CLNM, and the threshold for the occurrence of CLNM in each group of age and tumor maximum diameter was determined by the area under the receiver operating characteristic (ROC) .Results:The proportion of CLNM in the isthmus group, near-isthmus group and the lateral lobe group were 39.4% (69/175), 35.8% (34/95) and 29.6% (329/1113), respectively ( χ2=7.84, P=0.020). The intra-group comparison showed that there were statistical differences between the isthmus group and the lateral lobe group ( χ2=6.90, P=0.011), and there were no statistical differences between the isthmus group and near-isthmus group ( χ2=0.35, P=0.601), and near-isthmus group and the lateral leaf group ( χ2=1.62, P=0.313). Univariate and multivariate analysis showed that male ( OR: 3.697) and age < 38.5 years ( OR: 4.727) were independent risk factors for CLNM in PTC in the Isthmus Group, while male ( OR: 2.193), without HT ( OR: 1.702), tumor maximum diameter > 6.5 mm ( OR: 2.535) and age < 45.5 years ( OR: 3.030) were independent risk factors for CLNM in PTC in the lateral lobe group. Conclusions:Male sex and age are independent risk factors for CLNM in isthmus and lateral lobe PTC, and uncomplicated HT and tumor maximum diameter are also independent risk factors for CLNM in lateral lobe PTC. The incidence of CLNM in PTC in the isthmus, near-isthmus and lateral lobes decreased sequentially, and PTC in the near isthmus can not be simply regarded as the isthmus or lateral lobe PTC, and the lymph nodes in the central area should be fully evaluated before surgery to provide individualized treatment.

Objective To explore the effects of oleanolic acid on NF-κB/caspase-9 signaling pathway in kidneys of rat with diabetic nephropathy.Methods The diabetic nephropathy model rats were established,and the model rats were randomly divided intooleanolic acid low,medium and high dose groups,metformin group,and model group,with another 12 healthy SD rats as control group.The levels of blood glucose were measured at weeks 1,2 and 3 post-drug administration,and blood lipid and 24h urine urinary microalbumin(UMA)were measured after entire drug administration.Furthermore,we also detected the renal histopathology of rats,apoptosis of renal tubular,glomerular cells,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and protein expression of NF-κB/caspase-9 signaling pathway.Results Compared with the control group,the model group demonstrated higher levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,higher proportion of apoptotic renal tubular and glomerular,and higher expressions of caspase-9 protein and p-NF-κB p65/NF-κB p65(P＜0.05).Compared with the model group,the pathological damage of renal tissue in the metformin group and oleanolic acid low,middle and high dose groups were alleviated,the levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,the proportion of apoptotic renal tubular and glomerular,and the expressions of caspase-9 proteins and p-NF-κB p65/NF-κB p65 were decreased,and these indexes in oleanolic acid groups showed a dose-dependent manner(P＜0.05).Conclusion Oleanolic acid can improve the metabolism of glucose and lipid,reduce the pathological damage of renal tissue,inhibit the apoptosis of renal tubular and glomerular,and inhibit the NF-κB/caspase-9 pathway in diabetic nephropathy rats.

Objective:To compare the dosimetric differences between a 3D-printed non-coplanar multi-channel applicator and traditional single-channel/co-planar multi-channel applicators in postoperative vaginal brachytherapy for early-stage endometrial cancer.Methods:CT scan data of 66 patients with stage I endometrial cancer, encompassing 100 3D brachytherapy CT imaging datasets, admitted to Department of Gynecologic Oncology of the Fourth Hospital of Hebei Medical University from December 2021 to June 2024 were retrospectively analyzed. Based on CT images and delineated structures, offline reconstructions of radiotherapy plans were performed for single-channel, coplanar multi-channel, and 3D-printed non-coplanar multi-channel applicators. These 3 radiotherapy plans were optimized, and the high-risk clinical target volume (HR-CTV) coverage (V 100 ≥90%) and doses to organs at risk (rectum, bladder) were compared. The prescription dose was standardized at 600 cGy, with constraints of rectal D 2 cm3 ≤420 cGy and bladder D 2 cm3 ≤480 cGy. Comparison among multiple groups was conducted by ANOVA. Bonferroni method was used to correct P-values for comparison between two groups. Results:When defined as HR-CTV D 90%≥600 cGy, bladder D 2 cm3 was (398.29±76.13)cGy and rectum D 2 cm3 was (402.10±49.77)cGy of the 3D-printed non-coplanar multi-channel group,which were significantly lower than those in the single-channel group [bladder D 2 cm3 (424.09±131.52) cGy, rectum D 2 cm3 (493.11±115.17) cGy] and coplanar group [bladder D 2 cm3 (461.28±134.84) cGy, rectum D 2 cm3 (508.75±119.02) cGy], respectively. When limiting bladder D 2 cm3≤480 cGy, rectal D 2 cm3 was (446.81±78.53 cGy) of the 3D-printed non-coplanar multi-channel group, which was significantly lower than those in the single-channel group [(589.71±153.91) cGy] and the coplanar group [(545.51±122.00) cGy], respectively. Meanwhile, HR-CTV V 100% (94.53%±3.42%) was higher than (91.19%±7.63%) in the coplanar group. When the rectal D 2 cm3 was ≤ 420 cGy, HR-CTV V 100% was (91.92%±4.04%) of the 3D-printed non-coplanar multi-channel group,which was significantly better than (79.23%±13.95%) in the single-channel group and (85.88%±6.86%) in the coplanar group, respectively. Conclusions:The 3D-printed non-coplanar multi-channel applicator significantly reduces bladder and rectal doses while enhancing target coverage, outperforming traditional single-channel and co-planar multi-channel applicators. This innovation provides an optimized solution for individualized precision radiotherapy.

Objective:Papillary thyroid carcinoma with a maximum tumor diameter of ≤1 cm was defined as papillary thyroid carcinoma (PTC). To explore the clinical risk factors of central lymph node metastasis (CLNM) in PTC at different locations.Methods:The clinical and pathological data of 1383 cases with solitary PTC in Hangzhou First People’s Hospital were retrospectively analyzed, and they were divided into isthmus group (175 cases), near-isthmus group (95 cases) and lateral lobe group (1113 cases) according to their tumor location. Univariate and multivariate analyses were used to analyze the relationship between gender, age, tumor maximum diameter, Hashimoto’s thyroiditis (HT) and CLNM, and the threshold for the occurrence of CLNM in each group of age and tumor maximum diameter was determined by the area under the receiver operating characteristic (ROC) .Results:The proportion of CLNM in the isthmus group, near-isthmus group and the lateral lobe group were 39.4% (69/175), 35.8% (34/95) and 29.6% (329/1113), respectively ( χ2=7.84, P=0.020). The intra-group comparison showed that there were statistical differences between the isthmus group and the lateral lobe group ( χ2=6.90, P=0.011), and there were no statistical differences between the isthmus group and near-isthmus group ( χ2=0.35, P=0.601), and near-isthmus group and the lateral leaf group ( χ2=1.62, P=0.313). Univariate and multivariate analysis showed that male ( OR: 3.697) and age < 38.5 years ( OR: 4.727) were independent risk factors for CLNM in PTC in the Isthmus Group, while male ( OR: 2.193), without HT ( OR: 1.702), tumor maximum diameter > 6.5 mm ( OR: 2.535) and age < 45.5 years ( OR: 3.030) were independent risk factors for CLNM in PTC in the lateral lobe group. Conclusions:Male sex and age are independent risk factors for CLNM in isthmus and lateral lobe PTC, and uncomplicated HT and tumor maximum diameter are also independent risk factors for CLNM in lateral lobe PTC. The incidence of CLNM in PTC in the isthmus, near-isthmus and lateral lobes decreased sequentially, and PTC in the near isthmus can not be simply regarded as the isthmus or lateral lobe PTC, and the lymph nodes in the central area should be fully evaluated before surgery to provide individualized treatment.

Objective To investigate the therapeutic effect,underlying mechanism,and key genes involved in tetramethylpyrazine-pretreated umbilical cord mesenchymal stem cell (ucMSC) transplantation in a rat model of ischemic stroke. Methods The rat MCAO model was established,and umbilical cord-derived mesenchymal stem cells (ucMSCs) pretreated with or without tetramethylpyrazine were transplanted via the tail vein. Neurological function scores,TTC staining,and infarct rates were assessed. Localization of ucMSCs in brain tissue was observed. Experimental groups were analyzed using chip technology,and sample data were standardized. Bioinfor-matics analysis was employed to identify differential genes,which were subsequently validated by PCR. Results The treatment effect in ucMSCs pretreated with tetramethylpyrazine group was significantly superior to that of the untreated group,as evidenced by a significant reduction in neurological function score,infarct rate,and infarct area observed through TTC staining. Moreover,the treated group exhibited a significantly higher number of ucMSCs located within brain injury tissues compared to the untreated group. Subsequently,2905 differential mRNA were screened based on predetermined criteria,including 1754 up-regulated and 1151 down-regulated genes. Among these differentially expressed genes related to the chemokine signaling pathway (identified using a multiple change value ≥ 2.0 and P value ≤ 0.05),we identified 27 genes of interest. Notably,our analysis revealed activation of four genes closely associated with cell migration:Ccr6,Ccr3,Cxcr1 and Ccl6 respectively. Random verification experiments further confirmed a significant increase in gene expression for both Ccr3 and Cxcr1. Conclusions Pretreatment of umbilical cord-derived mesenchymal stem cells (ucMSCs) with tetramethylpyrazine significantly augmented the therapeutic efficacy in a rat model of ischemic stroke. Following pretreatment,there was a substantial increase in the migration of ucMSCs towards the site of brain injury. Our analysis suggests that this effect may be attributed to the activation of multiple chemokines,including Ccr6,Ccr3,Cxcr1,and Ccl6,by tetramethylpyrazine.

Objective:To clarify the effects of simple subtalar fusion on distribution of plantar pressures.Methods:A retrospective study was conducted to analyze the 19 patients who had undergone simple subtalar fusion between January 2006 and December 2020 at Department of Orthopedics, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. There were 13 males and 6 females with an age of (42.1±11.8) years and a duration of disease of 1.7 (1.0, 2.0) years. Another 14 normal subjects were recruited as normal controls [7 males and 7 females, with an age of (25.0±1.9) years]. The data of plantar pressure distribution were detected and analyzed by a Belgian Footscan? plantar pressure tester. The affected and healthy sides of the patients were compared with those of the normal group to analyze the peak pressures on different foot regions.Results:There was no significant difference in height or weight between the patients and the normal subjects ( P>0.05). The peak pressures on the first to the third metatarsal region of the forefoot and the medial region of the hindfoot of the affected foot were significantly lower than those of the normal foot in the patients ( P<0.05). The peak pressure on the forefoot region of a normal foot appeared in the third metatarsal region. In the patients, the peak pressure on the forefoot region of a healthy side shifted inward and appeared in the second metatarsal region, but the peak pressure on the forefoot region of an affected side shifted laterally and appeared in the fourth metatarsal region. The peak pressure on the midfoot of an affected side [(4.38±2.17) N/cm 2] was significantly higher than that on a healthy side [(3.04±1.80) N/cm 2] in the patients ( P=0.035). The peak pressures on the medial and lateral hindfoot regions of a healthy side were (7.12±1.91) N/cm 2 and (7.98±2.03) N/cm 2, respectively, showing no significant difference ( P=0.086). The peak pressure on the lateral hindfoot region of an affected side [(10.77±4.21) N/cm 2] was significantly higher than that on the medial hindfoot region [(8.71±2.89) N/cm 2] ( P=0.009). The peak plantar pressures on the affected side shifted to the lateral side in the patients. Conclusions:Subtalar fusion can exert significant effects on the distribution of plantar pressures. Specifically, the plantar pressures shift to the lateral side of an affected foot during all the gait stages while the plantar pressures on the healthy forefoot may compensate by transferring to the medial side in the patients.

Objective To investigate the therapeutic effect,underlying mechanism,and key genes involved in tetramethylpyrazine-pretreated umbilical cord mesenchymal stem cell (ucMSC) transplantation in a rat model of ischemic stroke. Methods The rat MCAO model was established,and umbilical cord-derived mesenchymal stem cells (ucMSCs) pretreated with or without tetramethylpyrazine were transplanted via the tail vein. Neurological function scores,TTC staining,and infarct rates were assessed. Localization of ucMSCs in brain tissue was observed. Experimental groups were analyzed using chip technology,and sample data were standardized. Bioinfor-matics analysis was employed to identify differential genes,which were subsequently validated by PCR. Results The treatment effect in ucMSCs pretreated with tetramethylpyrazine group was significantly superior to that of the untreated group,as evidenced by a significant reduction in neurological function score,infarct rate,and infarct area observed through TTC staining. Moreover,the treated group exhibited a significantly higher number of ucMSCs located within brain injury tissues compared to the untreated group. Subsequently,2905 differential mRNA were screened based on predetermined criteria,including 1754 up-regulated and 1151 down-regulated genes. Among these differentially expressed genes related to the chemokine signaling pathway (identified using a multiple change value ≥ 2.0 and P value ≤ 0.05),we identified 27 genes of interest. Notably,our analysis revealed activation of four genes closely associated with cell migration:Ccr6,Ccr3,Cxcr1 and Ccl6 respectively. Random verification experiments further confirmed a significant increase in gene expression for both Ccr3 and Cxcr1. Conclusions Pretreatment of umbilical cord-derived mesenchymal stem cells (ucMSCs) with tetramethylpyrazine significantly augmented the therapeutic efficacy in a rat model of ischemic stroke. Following pretreatment,there was a substantial increase in the migration of ucMSCs towards the site of brain injury. Our analysis suggests that this effect may be attributed to the activation of multiple chemokines,including Ccr6,Ccr3,Cxcr1,and Ccl6,by tetramethylpyrazine.

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.

Objective To obtain the data of radiological diagnosis and treatment resource distribution at medical institutions of different levels and in various cities, understand the status of resource allocation, provide policy-making basis and suggestions for optimizing the allocation of radiological diagnosis and treatment resources within the province, and offer data and references for related research. Methods A basic situation questionnaire survey was conducted on radiological diagnosis and treatment institutions in Hunan Province. Data were reviewed, analyzed, and statistically processed using Excel software to understand the allocation situation of radiological diagnosis and treatment resources in Hunan Province. Results As of 2022, there were 3031 radiological diagnosis and treatment institutions, 19770 radiation workers, and 6617 pieces of radiological diagnostic and treatment equipment. There were 80 radiation treatment institutions, 49 nuclear medicine institutions, 178 interventional radiology institutions, and 3028 X-ray imaging diagnosis institutions. There were 1077 radiation workers in radiation treatment, 461 radiation workers in nuclear medicine, 3369 radiation workers in interventional radiology, and 14,863 radiation workers in X-ray imaging diagnosis. There were 135 pieces of radiation treatment equipment, 56 pieces of nuclear medicine equipment, 262 pieces of interventional radiology equipment, and 6164 pieces of X-ray imaging diagnosis equipment. Conclusion Primary and lower grade medical institutions in Hunan Province account for a relatively high proportion of the total number of medical institutions, whereas radiological diagnostic and treatment resources are predominantly concentrated in tertiary medical institutions, demonstrating a unbalanced allocation of radiological diagnosis and treatment resources in various cities. In terms of the overall allocation of radiological diagnosis and treatment resources, interventional radiology is superior to the national average, nuclear medicine and X-ray imaging diagnosis are comparable to the national averages, and radiation treatment is lower than the national average. The total GDP is not the decisive factor in determining the development of local medical levels. It is suggested that relevant authorities should improve the rationality of the planning for the allocation of radiological diagnosis and treatment resources, promote the allocation of radiological diagnosis and treatment resources to the grassroots and underdeveloped areas through various measures, and thus achieve the goal of balanced resource allocation.