Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.

Objective:To investigate risk factors for permanent hypoparathyroidism (PHPP) after total thyroidectomy in patients with differentiated thyroid carcinoma (DTC).Methods:The clinical data of 316 DTC patients who underwent total thyroidectomy at our hospital from Jan 2020 to Jan 2023 were retrospectively analyzed. Patients were divided into normal parathyroid function group (284 cases) and hypoparathyroidism group (32 cases) according to whether parathyroid function was decreased. The clinical examination, intraoperative conditions and postoperative pathological data of the two groups were statistically analyzed.Results:Logistic regression analysis showed that: serum calcium on the first postoperative day ( OR=0.163, P<0.05), parathyroid hormon (PTH) on the first postoperative day ( OR=0.958, P<0.05), bilateral lymph node dissection ( OR=3.138, P<0.05), accidental resection of parathyroid (PG) ( OR=2.614, P<0.05), posterior capsule tumor invasion ( OR=3.336, P<0.05) and multiple cancer foci ( OR=2.664, P<0.05) were independent risk factors for PHPP after total thyroidectomy. Conclusion:Postoperative day 1 serum calcium, postoperative day 1 PTH, bilateral lymph node dissection, accidental resection of PG, posterior capsule invasion and multiple cancer foci are independent risk factors for PHPP after total thyroidectomy.

Paying for TCM according to the value of efficacy is an intrinsic requirement for establishing an effective and efficient diversified medical insurance payment method, and is also an important measure to support the inheritance, innovation and development of TCM. This study used text mining and PMC index model to quantitatively analyze and evaluate the texts of 20 special policies on payment based on efficacy value in TCM. It was found that there were 6 excellent policies, 14 acceptable policies, and there were no undesirable policies or perfect policies; overall, the average policy PMC index was 6.94, and the average provincial policy was 7.06, which was higher than the prefecture-level average of 6.27; the overall quality of special policies of TCM based on efficacy value was relatively high, but there was still much room for improvement in terms of policy timeliness, policy evaluation, policy measures, policy tools, and balance of policy design between provinces and cities.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

Objective:To investigate the factors influencing the metastasis of right-sided lymph nodes posterior to right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid microcarcinoma (PTMC) at cN 0 stage, to construct a nomogram prediction model for metastasis of right-sided LN-prRLN in patients with PTMC at cN 0 stage and to provide the decision reference for the dissection of right-sided LN-prRLN. Methods:A retrospective case-controlled study was conducted. The clinical data of patients receiving right-sided LN-prRLN dissection in Baoding No.1 Central Hospital between January 2023 and June 2024 were collected. All patients were divided into the metastatic group and the normal group according to whether metastasis of right-sided LN-prRLN would happen after the postoperative pathological examination. The differences in the clinicopathological characteristics between the 2 groups were compared, and multivariate logistic regression model was used to screen out the independent risk factors influencing right-sided LN-prRLN. A nomogram prediction model for metastasis of right-sided LN-prRLN based on independent risk factors was built; taking the postoperative pathological examination results as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model in determining the metastasis of right-sided LN-prRLN. Bootstrap internal validation method was used for random sampling to calculate the consistency index (CI) of the model. The calibration curves and clinical decision curves were drawn to respectively verify the calibration degree of the model and the clinical application ability of the model.Results:All 235 patients included 57 males (24.3%) and 178 females (75.7%). The age was (39±13) years old and 47 cases (20.0%) out of 235 patients had the metastasis of right-sided LN-prRLN. The proportion of patients characterized by male, right-sided tumors, tumor diameter > 0.5 cm, extrathyroidal invasion, metastasis of right-sided lymph nodes anterior to right recurrent laryngeal nerve (LN-arRLN) in the metastatic group was higher than that in the normal group, and the differences were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that male ( OR = 3.705, 95% CI: 1.133-12.116, P = 0.030), right-sided tumors ( OR = 5.610, 95% CI: 1.811-17.381, P = 0.003), the increased tumor diameter ( OR = 3.504, 95% CI: 1.169-10.507, P = 0.025), extrathyroidal invasion ( OR = 2.812, 95% CI: 1.026-7.708, P = 0.044) and right-sided LN-arRLN metastasis ( OR = 10.522, 95% CI: 3.237-34.199, P < 0.001) were independent risk factors of the metastasis of LN-prRLN in PTMC patients at cN 0 stage; based on the above independent risk factors, a nomogram prediction model was established. The ROC curve showed that the area under the curve of the nomogram prediction model for determining the metastasis of right-sided LN-prRLN in PTMC patients at cN 0 stage was 0.864 (95% CI: 0.794-0.935), Youden index was 0.735, the optimal cut-off value was 4.562, the corresponding sensitivity was 87.0%, and the corresponding specificity was 86.5%, which indicated a high predictive value of the nomogram model. Bootstrap test internal validation showed that the CI was 0.810 (95% CI: 0.763-0.917). Calibration curves showed that bias-corrected line was close to the ideal line, indicating a good consistency ( P = 0.347). Decision curve showed a good clinical efficacy. Conclusions:Male, right-sided tumors, the increased tumor diameter, extrathyroidal invasion and right-sided LN-arRLN metastasis are independent risk factors for right-sided LN-prRLN metastases in patients with PTMC at cN 0 stage. The nomogram prediction model based on the above factors has a good predictive performance, which is helpful for surgeons to make clinical decisions.

Objective:To investigate risk factors for permanent hypoparathyroidism (PHPP) after total thyroidectomy in patients with differentiated thyroid carcinoma (DTC).Methods:The clinical data of 316 DTC patients who underwent total thyroidectomy at our hospital from Jan 2020 to Jan 2023 were retrospectively analyzed. Patients were divided into normal parathyroid function group (284 cases) and hypoparathyroidism group (32 cases) according to whether parathyroid function was decreased. The clinical examination, intraoperative conditions and postoperative pathological data of the two groups were statistically analyzed.Results:Logistic regression analysis showed that: serum calcium on the first postoperative day ( OR=0.163, P<0.05), parathyroid hormon (PTH) on the first postoperative day ( OR=0.958, P<0.05), bilateral lymph node dissection ( OR=3.138, P<0.05), accidental resection of parathyroid (PG) ( OR=2.614, P<0.05), posterior capsule tumor invasion ( OR=3.336, P<0.05) and multiple cancer foci ( OR=2.664, P<0.05) were independent risk factors for PHPP after total thyroidectomy. Conclusion:Postoperative day 1 serum calcium, postoperative day 1 PTH, bilateral lymph node dissection, accidental resection of PG, posterior capsule invasion and multiple cancer foci are independent risk factors for PHPP after total thyroidectomy.

Objective:To investigate the factors influencing the metastasis of right-sided lymph nodes posterior to right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid microcarcinoma (PTMC) at cN 0 stage, to construct a nomogram prediction model for metastasis of right-sided LN-prRLN in patients with PTMC at cN 0 stage and to provide the decision reference for the dissection of right-sided LN-prRLN. Methods:A retrospective case-controlled study was conducted. The clinical data of patients receiving right-sided LN-prRLN dissection in Baoding No.1 Central Hospital between January 2023 and June 2024 were collected. All patients were divided into the metastatic group and the normal group according to whether metastasis of right-sided LN-prRLN would happen after the postoperative pathological examination. The differences in the clinicopathological characteristics between the 2 groups were compared, and multivariate logistic regression model was used to screen out the independent risk factors influencing right-sided LN-prRLN. A nomogram prediction model for metastasis of right-sided LN-prRLN based on independent risk factors was built; taking the postoperative pathological examination results as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model in determining the metastasis of right-sided LN-prRLN. Bootstrap internal validation method was used for random sampling to calculate the consistency index (CI) of the model. The calibration curves and clinical decision curves were drawn to respectively verify the calibration degree of the model and the clinical application ability of the model.Results:All 235 patients included 57 males (24.3%) and 178 females (75.7%). The age was (39±13) years old and 47 cases (20.0%) out of 235 patients had the metastasis of right-sided LN-prRLN. The proportion of patients characterized by male, right-sided tumors, tumor diameter > 0.5 cm, extrathyroidal invasion, metastasis of right-sided lymph nodes anterior to right recurrent laryngeal nerve (LN-arRLN) in the metastatic group was higher than that in the normal group, and the differences were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that male ( OR = 3.705, 95% CI: 1.133-12.116, P = 0.030), right-sided tumors ( OR = 5.610, 95% CI: 1.811-17.381, P = 0.003), the increased tumor diameter ( OR = 3.504, 95% CI: 1.169-10.507, P = 0.025), extrathyroidal invasion ( OR = 2.812, 95% CI: 1.026-7.708, P = 0.044) and right-sided LN-arRLN metastasis ( OR = 10.522, 95% CI: 3.237-34.199, P < 0.001) were independent risk factors of the metastasis of LN-prRLN in PTMC patients at cN 0 stage; based on the above independent risk factors, a nomogram prediction model was established. The ROC curve showed that the area under the curve of the nomogram prediction model for determining the metastasis of right-sided LN-prRLN in PTMC patients at cN 0 stage was 0.864 (95% CI: 0.794-0.935), Youden index was 0.735, the optimal cut-off value was 4.562, the corresponding sensitivity was 87.0%, and the corresponding specificity was 86.5%, which indicated a high predictive value of the nomogram model. Bootstrap test internal validation showed that the CI was 0.810 (95% CI: 0.763-0.917). Calibration curves showed that bias-corrected line was close to the ideal line, indicating a good consistency ( P = 0.347). Decision curve showed a good clinical efficacy. Conclusions:Male, right-sided tumors, the increased tumor diameter, extrathyroidal invasion and right-sided LN-arRLN metastasis are independent risk factors for right-sided LN-prRLN metastases in patients with PTMC at cN 0 stage. The nomogram prediction model based on the above factors has a good predictive performance, which is helpful for surgeons to make clinical decisions.