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.

Glycosylation plays an important role in tumorigenesis and development. Mucoprotein-1 (MUC1), a transmembrane glycoprotein, is overexpressed in a variety of malignant tumors. The biochemical characteristics of tumor-specific short chain O-glycosylation (such as Tn/sialyl Tn (STn) antigens) are significantly different from those of normal tissue MUC1, which provides a molecular basis for precision diagnosis and treatment of tumors. This article systematically reviews the molecular design, clinical transformation progress and technical bottleneck of three types of probes targeting MUC1 glycosylation epitopes in tumors, including aptamers, peptides and monoclonal antibodies, focusing on their tumor uptake efficiency, targeting specificity and the potential of diagnosis and treatment integration, so as to provide theoretical basis for optimizing the clinical transformation path of MUC1 targeting probes.

Objective To investigate the clinical and diffusion imaging of brain damage in patients with neurosyphilis.Methods Eighty patients with neurosyphilis with brain damage were retrospectively selected as the study group,and were divided into mild group(n=38)and moderate to severe group(n=42)according to imaging results.Another 80 healthy subjects in the same period were selected as the control group.The values of apparent diffusion coefficient(ADC)and fractional anisotropy(FA)were compared among the three groups.Pearson test was used to analyze the correlation between ADC and FA values in various brain regions and cognitive function in patients with neurosyphilis brain damage.Results ADC values in parieto-occipital lobe,frontal lobe,basal gan-glia and hemioval center in moderate to severe group were significantly higher than those in mild group and control group,and FA values were significantly lower than those in mild group and control group(P<0.05).The results of Pearson analysis showed that the ADC and FA values of parieto-occipital lobe,frontal lobe and hemioval center were significantly correlated with Wechsler adult intel-ligence scale-revised of China(WAIS-RC)knowledge,WAIS-RC arithmetic,verbal fluency test(VFT),Montreal cognitive assess-ment(MoCA),forward digit span test(FDST),trail making test A(TMT-A)and trail making test B(TMT-B)scores(P<0.05).Conclusion The ADC and FA values of parieto-occipital lobe,frontal lobe,basal ganglia and hemioval center are closely related to the severity of brain damage,which is helpful for clinical diagnosis.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

Objective　To investigate the level of pertussis antibody in 344 healthy population in Hebei Province in 2023, and to understand the infection status and estimate the potential infection of pertussis. Methods　A total of 344 healthy people of all ages from 7 cities (counties) in Hebei Province in 2023 were stratified by random sampling method. The demographic characteristics, vaccination history and pertussis history of the subjects were collected. Serum IgG antibody against pertussis toxin (PT-IgG) were determined by enzyme-linked immunosorbent assay (ELISA). Results　The geometric mean concentration (GMC) of PT-IgG in 344 healthy people was 5.28 IU/mL, and the antibody positive rate (PT-IgG concentration ≥ 40 IU/mL) was 6.10% (21/344). There was no significant difference in proportion of antibody levels and antibody concentration ≥40 IU/mL between males and females. The top three regions with the highest antibody positive rate were Xinhe County in Xingtai (20.00%), Lianchi District in Baoding (11.43%), and Shijiazhuang (9.37%). There was a significant difference in pertussis antibody levels among different regions (P=0.007), but no significant difference in pertussis antibody concentration ≥40 IU/mL among different regions (P=0.100). The GMC of antibody was the highest in the 1~<3 years old group (11.45 IU/mL), followed by the <1 year old group (8.15 IU/mL). There was a significant difference in the pertussis antibody levels among different age groups (P=0.001). The proportion of antibody concentration ≥40 IU/mL was the highest in the 1~<3 years old group (20.83%), followed by the <1 year old group (12.77%). There was a significant difference in the proportion of antibody concentration ≥40 IU/mL among different age groups (P=0.028). And 303 (88.08%) cases of the 344 healthy people had a history of DTaP , 4.62%, 46.86% and 48.52% of healthy people had completed 1-2 , 3 and 4 doses of DTaP, respectively. Among the healthy people who had completed 1-2 doses of DTaP, there was no significant difference in the level of pertussis antibody among different age groups (P=0.47). Among the healthy people who had completed 3 doses of basic immunization and 4 doses of complete immunization, there was a significant difference in the level of pertussis antibody among different age groups (P=0.04, P=0.01). There was no significant difference in the proportion of PT-IgG concentration ≥40 IU/mL among different age groups and different immunization doses (P=0.72). Conclusion　The overall antibody level and proportion of PT-IgG concentration ≥40 IU/mL in the healthy population of Hebei Province in 2023 were both low, indicating the inadequacy of the protective effect of the current immunization program for children, although vaccinated people could still infect with pertussis disease, we need to further monitoring and optimization of immune strategies indicating.

Objective:A mineralized gelatin methacryloyl/hyaluronic acid methacryloyl (GelMA/HAMA) double network hydrogel was constructed, its performance was characterized, and its cell compatibility was studied.Methods:The hydrogel was constructed by photocrosslinking technology, and the biomimetic mineralized hydrogel was prepared by alternating mineralization with calcium and phosphorus solution. The hydrogel was mineralized for three times, for 24 h each time. The control groups were the non-mineralized groups, named the GelMA-0 group and GelMA/HAMA-0 group, respectively. The experimental groups were the mineralized treatment groups. The GelMA hydrogel and GelMA/HAMA double network hydrogel mineralized for 1, 2 and 3 times were named the GelMA-1, 2 and 3 group and GelMA/HAMA-1, 2 and 3 group, respectively. The microstructure of the mineralized hydrogel was characterized by scanning electron microscope and energy dispersive X-ray spectroscopy. The chemical composition of the mineralized hydrogel was characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The mineralization rate of the mineralized hydrogel was evaluated by the ashing method. The compressive strength of the mineralized hydrogel was evaluated by a compression test. The cell compatibility of bone marrow mesenchymal stem cells (BMSCs) on the mineralized hydrogel surface was evaluated by a cell counting kit-8 assay and living/dead cell staining experiment. The datas were analyzed by one-way analysis of variance and Tukey test.Results:With the increase in the number of mineralization cycles, the mineralized layer gradually thickened, and the mineral layer on the cross section of the hydrogel uniformly penetrated into the interior of the hydrogel, with the amount of internal mineral deposition increased. The microstructure of the hydrogel and the distribution of inorganic particles also changed. The surface of the GelMA-3 group and the GelMA/HAMA-3 group contained Ca and P elements, and the distribution was consistent. The inorganic particles generated by mineralization may be immature hydroxyapatite (HAP) crystal precursors. To further verify the chemical composition of inorganic particles, the GelMA-0 and 3 groups as well as the GelMA/HAMA-0 and 3 groups of hydrogels showed GelMA amide Ⅰ, Ⅱ and Ⅲ bands. The GelMA-3 group and GelMA/HAMA-3 group hydrogels contained phosphate, and the diffraction peaks confirmed that the inorganic particles are mainly HAP crystal precursors with low crystallinity. The mineralization rates of the GelMA-1, 2 and 3 groups were (12.48±1.06)%, (21.12±0.62)% and (27.31±0.45)%, while those of the GelMA/HAMA-1, 2 and 3 groups were (15.54±1.03)%, (23.39±0.25)% and (32.26±0.62)%, and the compressive elastic modulus of the GelMA-0, 1, 2 and 3 groups were (69.01±1.04, 91.76±2.05, 105.16±2.95, 131.65±2.21) kPa, and those of the GelMA/HAMA-0, 1, 2 and 3 groups were (270.76±4.56, 347.47±4.60, 388.98±6.96, 430.6±15.47) kPa. Under the same cyclic mineralization times, the mineralization rates and compressive elastic modulus of the GelMA/HAMA double network hydrogel were significantly higher than those of the GelMA hydrogel (all P<0.01). The cell proliferation rates of BMSCs on the GelMA/HAMA-0, 1, 2 and 3 hydrogel surfaces were (49.80±3.38)%, (52.32±1.28)%, (58.00±4.64)% and (62.46±2.74)% on the first day of culture, (58.86±3.36)%, (58.26±3.45)%, (73.08±2.61)% and (76.40±3.45)% on the third day of culture, and (85.89±4.23)%, (90.75±3.21)%, (103.35±4.11)% and (113.42±3.40)% on the fifth day of culture. The cell proliferation rates of the GelMA/HAMA-3 group were significantly higher than those of GelMA/HAMA-0 and 1 groups (all P<0.01). Living/dead cell staining experiment showed that BMSCs on the surface of the GelMA/HAMA-0, 1, 2 and 3 groups were dominated by living cells on the third and fifth days of culture. Conclusions:The mineralized GelMA/HAMA double network hydrogel was constructed, which significantly improved the mineralization rate, mechanical performance and cell compatibility of the biomimetic mineralized hydrogel.

In vivo, cells exist within the mechanical microenvironment of the extracellular matrix (ECM), and their biological processes are regulated by various mechanical factors. However, existing technology limits the direct study of the interaction between cells and ECM in vivo. Using hydrogel to mimic the natural ECM and to construct a suitable mechanical microenvironment for isolated cells, which indirectly reflects the cell-ECM interactions in real organisms through in vitro studies. Thus, in this review, the effects of mechanical factors in hydrogel on different types of cells were summarized, and the development of cell mechanical detection technology using hydrogel as carriers was introduced. Moreover, the future work of using hydrogel to study cell mechanical behavior and related detection technology, as well as standardized preparation, was discussed.

Dynamic hydrogel is three-dimensional networks of hydrophilic polymer formed by dynamic reversible cross-linked bonds. It is widely used in the field of bone repair therapy. The dynamic reversible cross-linked bonds in the dynamic hydrogel endows it with shear-thinning rheological properties, resulting in excellent self-healing, injectability and tunable mechanical properties. In this review, the formation mechanism of dynamic hydrogel was summarized, including non-covalent interaction and dynamic covalent interaction. The advantages and disadvantages of the various cross-linked methods used to form dynamic hydrogel were discussed. The applications of dynamic hydrogel in bone repair therapy were summarized, including haemostasis for filling bone defects, drug delivery, modulation of stem cell behavior, and biomimetic mineralization, to provide a reference for the future development of dynamic hydrogel for bone repair therapy.