ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

The promulgation of the Technical Specifications for Clinical Use of Blood (2025 Edition) signifies that China's clinical blood transfusion management has transitioned from mere technical operations to a new stage centered on patient blood management (PBM). Through an in-depth comparison of the new and old specifications, this paper analyzes the core transformations regarding conceptual reconstruction, legal alignment, technological upgrades, and closed-loop management. The new specifications establish PBM principles, reinforce legal safeguards for informed consent and emergency treatment, and construct a comprehensive, refined quality control system by specifying compatibility testing standards and introducing a post-transfusion evaluation system. Medical institutions should seize this opportunity to update management protocols and information systems, deepen multidisciplinary collaboration, and drive the profound transformation of clinical blood use from focusing solely on safety assurance to placing equal emphasis on science and value.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective:To compare the impacts of external fixation of different durations on rehabilitation outcomes after open repair of acute Achilles tendon rupture.Methods:A prospective cohort study was conducted to analyze the clinical data of patients with unilateral acute closed Achilles tendon rupture admitted to Peking University Third Hospital from August 2020 to August 2023. Patients were divided into Group A ( n=96), Group B ( n=347), Group C ( n=346), and Group D ( n=105) based on different postoperative immobilization durations (0, 2, 4 and 6 weeks, respectively). After all the patients received identical open repair procedure, Group A was rehabilitated immediately but the other groups were rehabilitated with the same protocol after removal of the external fixation. Four groups were compared in terms of recovery time of one-leg heel-rise height (OHRH), recovery time of light exercise (LE) in brisk walking and jogging and recovery time of range of motion (ROM). Visual analogue scale (VAS) scores were also compared at 2, 4, 6 and 8 weeks postoperatively. Achilles tendon total rupture score (ATRS) and American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores were evaluated at 6, 8, 10, 12, 14 and 16 weeks postoperatively. Complications were recorded. Results:A total of 894 patients including 869 males and 25 females were included, aged 18-60 years [(35.0±6.3)years]. All the patients were followed up for 14-25 months [(19.0±3.0)months]. The recovery time of OHRH in Group A and B was 12.0(12.0, 12.0)weeks and 12.0(10.0, 12.0)weeks, shorter than those in Group C [14.0(14.0, 16.0)weeks] and D [14.0(14.0, 14.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of LE in Group A and B was 18.0(18.0, 18.0)weeks and 18.0(16.0, 18.0)weeks, shorter than those in Group C [20.0(20.0, 20.0)weeks] and D [20.0(20.0, 20.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of ROM in Group A and B was 6.0(6.0, 6.0)weeks and 6.0(6.0, 6.0)weeks, shorter than those in Group C [8.0(8.0, 10.0)weeks] and D [10.0(10.0, 10.0)weeks)] ( P<0.05), with no significant difference between Group A and B, and between Group C and D ( P>0.05). At 2 weeks postoperatively, the VAS scores were 2.0(1.0, 2.0)points, 2.0(1.0, 2.0)points, and 2.0(1.5, 2.0)points in Group B, C and D, lower than 5.0(5.0, 5.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 4 weeks postoperatively, the VAS scores were 1.0(0, 1.0)points, 1.0(0, 1.0)points, and 1.0(0.5, 1.0)points in Group B, C and D, lower than 2.0(1.0, 2.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 6 weeks postoperatively, the VAS score was 0(0, 0)points in all the 4 groups, with no significant difference among them ( P>0.05). At 8 weeks postoperatively, the VAS score was 0(0, 0)points, with lower scores in Group A and B than those in Group C and D ( P<0.05) but with no significant difference between Group A and B and between Group C and D ( P>0.05). At 6 weeks postoperatively, the ATRS scores were 52.0(52.0, 53.8)points and 52.0(50.0, 53.0)points in Group A and B, higher than 41.0(38.0, 43.0)points and 19.0(18.0, 20.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the ATRS scores were 66.0(66.0, 68.0)points in Group A, higher than 63.0(62.0, 64.0)points, 52.0(50.0, 53.0)points, and 39.0(37.0, 40.0)points in Group B, C and D ( P<0.05), with a higher score in Group B than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the ATRS score was 75.0(74.0, 76.0)points in Group B, higher than 69.0(69.0, 70.0)points, 72.0(66.0, 74.0)points, and 62.0(58.5, 63.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the ATRS score was 84.0(82.0, 85.0)points in Group B, higher than 75.0(75.0, 77.0)points, 79.0(72.0, 81.0)points, and 72.0(71.0, 73.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 14 weeks postoperatively, the ATRS score was 87.0(86.0, 87.0)points in Group B, higher than 82.0(82.0, 84.0)points, 83.0(80.0, 85.0)points, and 79.0(77.5, 80.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 16 weeks postoperatively, the ATRS scores were 87.0(87.0, 88.0)points and 88.0(87.0, 88.0)points in Group A and B, higher than 86.0(85.0, 87.0)points and 84.0(83.0, 85.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 6 weeks postoperatively, the AOFAS ankle-hindfoot scores were 94.0(94.0, 95.0)points and 95.0(94.0, 96.0)points in Group A and B, higher than 85.0(83.0, 86.0)points and 74.0(72.0, 75.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the AOFAS ankle-hindfoot scores were 100.0(99.0, 100.0)points in Group B, higher than 94.0(94.0, 95.0)points, 92.0(90.0, 93.0)points, and 83.0(82.0, 84.0)points in Group A, C and D ( P<0.05), with a higher score in Group A than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in Group B, higher than 98.0(98.0, 98.0)points, 98.0(96.8, 99.0)points, and 96.0(95.0, 97.0)points in Group A, C and D, with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in both Group A and B, with no significant difference between them ( P>0.05), which was higher than 100.0(98.0, 100.0)points and 99.0(98.0, 99.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05). At 14 and 16 weeks postoperatively, AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points, with no significant difference among all the groups ( P>0.05). Superficial wound infection occurred in 12 patients [5.2%(5/96) in Group A, 0.6%(2/347) in Group B, 0.6%(2/346) in Group C and 2.9%(3/105) in Group D] ( P<0.01) while rerupture occurred in 16 [9.4%(9/96) in Group A, 1.2% (4/347) in Group B, 0.9%(3/105) in Group C, and 0 patient in Group D] ( P<0.01). Conclusion:For patients with unilateral acute Achilles tendon rupture, two weeks of postoperative external fixation after open repair can shorten the time of returning sports, alleviate pain, and promote functional recovery, without increasing the risk of complications.

Objective:To report the follow-up status of patients participating phase Ⅲ clinical trial (ZGDD3) of Donafenib tosilate (abbreviated as Donafenib) in the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), and to explore its efficacy, safety and prognostic factors.Methods:This study was a randomized controlled trial, and the clinicopathological data and follow-up results of 29 patients (16 males, 13 females, age 40-68 years) who participated in the clinical trial ZGDD3 between August 2018 and March 2021 were analyzed. Patients were divided into Donafenib group and placebo group using the central dynamic randomization method with the ratio of 2∶1. Adverse reactions (AE) during the trial were observed. Independent-sample t test, Mann-Whitney U test and Fisher exact test were used to analyze the differences of baseline characteristics between the two groups. Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier method was used to draw the survival curve (log-rank test) and Cox regression analysis was used to analyze the prognostic factors. Results:There were 22 patients in Donafenib group and 7 patients in placebo group. There were no significant differences of baseline characteristics between the two groups ( t values: -0.68, Z values: from -1.47 to -0.56, all P>0.05). The follow-up was 32.07(21.07, 49.85) months. During the trial, drug-related AEs occurred in all patients in Donafenib group, mostly was grade Ⅰ-Ⅱ, no grade Ⅳ or Ⅴ AEs were found. The median PFS was significantly longer in Donafenib group than that in placebo group (13.23 vs 4.03 months; χ2=9.68, P=0.002), and the median OS was 55.00 and 24.30 months respectively ( χ2=2.07, P=0.150). Metastasis to less common sites was the independent risk factor for OS (hazard ratio ( HR)=6.789, 95% CI: 1.272-36.246, P=0.025). Conclusions:Donafenib shows good clinical application in the treatment of RAIR-DTC, demonstrating good safety and efficacy. Metastasis to less common sites is closely related to OS.