Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective To predict the constitutive parameters of a superelastic model of plantar soft tissues based on random forest(RF)and backpropagation(BP)neural network algorithms to improve the efficiency and accuracy of the method for obtaining constitutive parameters.Methods First,a finite element model for a spherical indentation experiment of plantar soft tissues was established,and the spherical indentation experiment process was simulated to obtain a dataset of nonlinear displacement and indentation force,divided into training and testing sets.The established RF and BP neural network(BPNN)models were trained separately.The constitutive parameters of plantar soft tissues were predicted using experimental data.Finally,the mean square error(MSE)and coefficient of determination(R2)were introduced to evaluate the accuracy of the model prediction,and the effectiveness of the model was verified by comparison with the experimental curves.Results Combining the RF and BPNN models with finite element simulation was an effective and accurate method for determining the superelastic constitutive parameters of plantar soft tissues.After training,the MSE of the RF model reached 1.370 2×10-3,and R2 was 0.982 9,whereas the MSE of the BPNN model reached 4.858 1×10-5,and R2 was 0.999 3.The inverse-determined constitutive parameters of the plantar soft tissues suitable for simulation were obtained.The calculated response curves for the two predicted sets of constitutive parameters were in good agreement with the experimental curves.Conclusions The prediction accuracy for the superelastic constitutive parameters of plantar soft tissues based on an artificial intelligence algorithm model is high,and the relevant research results can be applied to study other mechanical properties of plantar soft tissues.This study provides a new method for obtaining the constitutive parameters of plantar soft tissues and helps to quickly diagnose clinical problems,such as plantar soft tissue lesions.

Objective To investigate the application of machine learning to predict the hemodynamic parameters of combined stenotic left coronary artery(LCA)aneurysms.Methods Parameterized modeling and simulation based on the geometric parameter range of combined stenosis LCA aneurysms in clinical statistics were conducted.The obtained simulation data was used as the dataset,and two common machine learning models were constructed and trained for optimization to predict two key hemodynamic parameters:wall shear stress(WSS)and pressure.By comparing and analyzing the performances of these models on the training and testing sets,the accuracy of each model was evaluated,and the effectiveness of the data-driven prediction of hemodynamic parameters for LCA aneurysms with concomitant stenosis was verified.Results The effectiveness of machine learning method in inverting the hemodynamic parameters of aneurysms was determined.For WSS prediction,the trained deep learning model and random forest model achieved mean squared error(MSE),mean absolute error(MAE),and determination coefficient R2 of 0.052 8,0.032 2,0.988 3,and 0.078 2,0.046 3,and 0.976 6,respectively.For pressure prediction,the accuracies of the deep learning models and random forest models were comparable,with MSE,MAE,and R2 of 4.67×10-6,3×10-4,0.999 7,and 1.07×10-5,5×10-4,and 0.999 3,respectively.Conclusions Machine learning methods show high accuracy in predicting the hemodynamic parameters of combined stenotic coronary artery aneurysm models.The predictive accuracy of the model,computational efficiency,and needs of the application scenarios need to be considered in machine learning prediction so that the appropriate model can be selected according to the specific situation.This study has clinical significance,helping doctors to more accurately evaluate a patient's condition and provide new ideas and method for the diagnosis and treatment of cardiovascular diseases.

Objective:To investigate the application and effect of frontal-orbital reconstruction and distraction osteogenesis in the treatment of Crouzon syndrome using three-dimensiond reconstruction mold (3D-RM).Methods:Retrospective analysis was performed on the clinical data of children with Crouzon syndrome who were treated in the Department of Burning and Plastic Surgery, Children’s Hospital of Nanjing Medical University from January 2018 to December 2021. These children were divided into two groups. The study group performed fronto-orbital reconstruction combined with distraction osteogenesis using 3D-RM, while the control group performed the surgery without using 3D-RM. Intraoperative blood loss, operation time, duration of hospital stay, complication rate, cranial index, frontal and orbital retraction rate and postoperative frontal and orbital contour were compared between the two groups. The independent sample t-test was used to compare the differences in intraoperative blood loss, operation duration, hospital stay, postoperative cranial index and fronto-orbital retraction rate between the two groups. The Chi-square test was used to compare the differences in the incidence of postoperative complications between the two groups. Results:The study group included 10 children, including 6 males and 4 females, ranging in age from 9 to 37 months, with an average age of 19 months. In the control group, 8 children were included, including 5 males and 3 females, ranging in age from 8 to 46 months, with an average age of 25 months. The study group was followed up for 12 to 36 months, with an average of 18 months, and the head shape was better improved. The control group was followed up for 12 to 30 months, with an average of 18 months. No serious complications occurred and the head deformity was improved. There were no significant differences in intraoperative blood loss, operation duration, hospital stay, cranial index, fronto-orbital retraction rate and complication rate between the two groups (all P>0.05). The forehead shape of the study group was more symmetrical than that of the control group, the difference was statistically significant ( P<0.05). Conclusion:The effect of frontal orbital reconstruction and distraction osteogenesis using 3D-RM in the treatment of Crouzon syndrome is positive, the head shape and orbit are significantly improved. There were no serious complications after operation. It can play a good auxiliary role in the operation.

Objective:To investigate the application and effect of frontal-orbital reconstruction and distraction osteogenesis in the treatment of Crouzon syndrome using three-dimensiond reconstruction mold (3D-RM).Methods:Retrospective analysis was performed on the clinical data of children with Crouzon syndrome who were treated in the Department of Burning and Plastic Surgery, Children’s Hospital of Nanjing Medical University from January 2018 to December 2021. These children were divided into two groups. The study group performed fronto-orbital reconstruction combined with distraction osteogenesis using 3D-RM, while the control group performed the surgery without using 3D-RM. Intraoperative blood loss, operation time, duration of hospital stay, complication rate, cranial index, frontal and orbital retraction rate and postoperative frontal and orbital contour were compared between the two groups. The independent sample t-test was used to compare the differences in intraoperative blood loss, operation duration, hospital stay, postoperative cranial index and fronto-orbital retraction rate between the two groups. The Chi-square test was used to compare the differences in the incidence of postoperative complications between the two groups. Results:The study group included 10 children, including 6 males and 4 females, ranging in age from 9 to 37 months, with an average age of 19 months. In the control group, 8 children were included, including 5 males and 3 females, ranging in age from 8 to 46 months, with an average age of 25 months. The study group was followed up for 12 to 36 months, with an average of 18 months, and the head shape was better improved. The control group was followed up for 12 to 30 months, with an average of 18 months. No serious complications occurred and the head deformity was improved. There were no significant differences in intraoperative blood loss, operation duration, hospital stay, cranial index, fronto-orbital retraction rate and complication rate between the two groups (all P>0.05). The forehead shape of the study group was more symmetrical than that of the control group, the difference was statistically significant ( P<0.05). Conclusion:The effect of frontal orbital reconstruction and distraction osteogenesis using 3D-RM in the treatment of Crouzon syndrome is positive, the head shape and orbit are significantly improved. There were no serious complications after operation. It can play a good auxiliary role in the operation.

Objective:To investigate the effect of intrafrontal-orbital distraction osteogenesis in the treatment for school-aged children with severe proptosis in Crouzon syndrome.Methods:We retrospectively analyzed the clinical data of school-aged children with Crouzon syndrome treated with intrafrontal orbital distraction osteotomy at the Children’s Hospital of Nanjing Medical University from January 2016 to February 2021, and counted and analyzed the clinical results, complications (cerebrospinal fluid leakage, infection, etc.), and surgical safety.Results:A total of 12 children, 9 males and 3 females, aged 6-12.1 years, with an average age of 7.1 years, were included; 4 were cranial, 6 were craniofacial, and 2 were other types. All were shown with obvious proptosis. The surgical procedure was successful. Follow-up ranged from 3 to 20 months, with a mean of 14 months. The postoperative distraction distance was (19.1±3.3) mm, ranging from 15.2 to 25.6 mm. And the mean cranial index (CI) before and after surgery were 97.5% and 80.0%, respectively, with good craniofacial appearance and better improvement of proptosis and posterior cranial flattening. There were no other complications but for one child with infection at the external site of the distraction rod.Conclusions:The effect of frontal-orbital distraction osteotomy in the treatment of Crouzon syndrome with severe proptosis in school-aged children was positive, with significant improvement in proptosis and low incidence of postoperative cerebrospinal fluid leakage and infection. This procedure is a good choice for older children with severe proptosis.

Objective:To investigate the effect of intrafrontal-orbital distraction osteogenesis in the treatment for school-aged children with severe proptosis in Crouzon syndrome.Methods:We retrospectively analyzed the clinical data of school-aged children with Crouzon syndrome treated with intrafrontal orbital distraction osteotomy at the Children’s Hospital of Nanjing Medical University from January 2016 to February 2021, and counted and analyzed the clinical results, complications (cerebrospinal fluid leakage, infection, etc.), and surgical safety.Results:A total of 12 children, 9 males and 3 females, aged 6-12.1 years, with an average age of 7.1 years, were included; 4 were cranial, 6 were craniofacial, and 2 were other types. All were shown with obvious proptosis. The surgical procedure was successful. Follow-up ranged from 3 to 20 months, with a mean of 14 months. The postoperative distraction distance was (19.1±3.3) mm, ranging from 15.2 to 25.6 mm. And the mean cranial index (CI) before and after surgery were 97.5% and 80.0%, respectively, with good craniofacial appearance and better improvement of proptosis and posterior cranial flattening. There were no other complications but for one child with infection at the external site of the distraction rod.Conclusions:The effect of frontal-orbital distraction osteotomy in the treatment of Crouzon syndrome with severe proptosis in school-aged children was positive, with significant improvement in proptosis and low incidence of postoperative cerebrospinal fluid leakage and infection. This procedure is a good choice for older children with severe proptosis.

Objective:To investigate clinical effects of the three-dimensional(3D) digital technique-assisted distraction osteogenesis in newborns with Pierre Robin sequence(PRS).Methods:The data of neonatal Pierre Robin sequence treated with 3D digital technique-assisted distraction osteogenesis in Children’s Hospital Affiliated to Nanjing Medical University from April 2017 to April 2020 was retrospectively analyzed. 3D digital technique was used to assist the pre-operative design and osteotomy navigation template was made with 3D printing technique to guide in the mandibular osteotomy. CT scans were obtained 3 months postoperatively to follow up the growth of mandible. The rates of recurrence, titanium nail falling, infection, secondary operation and nerve injury were statistically analyzed. The counting data were analyzed using chi-square test. The independent influencing factors of postoperative complications were analyzed by multiple logistic regression, and the difference was statistically significant when P<0.05. Results:Three hundred and forty-five patients were included in the 3D digital technique group consisting of 215 males and 130 females with the ages ranged 3-28 days and the weights 1.8-3.2 kg. Surgical results were satisfied and very close to the preoperative design. Craniofacial CT results showed normal growth of mandible 3 months postoperatively. Three hundred and seventy-seven patients were included in the controlled group consisting of 230 males and 147 females with the ages ranged 6-28 days and the weights 1.6-3.6 kg. The recurrence rate, extender titanium nail off rate, reoperation rate and risk of nerve damage in the 3D digital technique group were 0.29%(1/345), 0.29%(1/345), 0.58% (2/345)and 0.29%(1/345), respectively, while in the control group, the numbers were 1.86%(7/377), 2.92%(11/377), 2.65%(10/377), 2.92% (11/377), respectively, which were significant lower than those in the 3D group. The infection rates were 7.83%(27/345) in the 3D digital technique group and 7.69%(29/377) in the control group, and there was no significant difference between the two groups. The results of multi-logistic regression analysis suggested that the 3D digital technique group could be an independent factor to reduce postoperative complications ( P=0.001). Conclusions:In the newborns with Pierre Robin sequence, 3D digital technique-assisted distraction osteogenesiscan significantly improve the accuracy and success rate of the operation and reduce the complication rate as well.