ObjectiveTo investigate the relationship between the vasodilation and hydrogen sulfide （H₂S） mechanism of total flavonoids of chrysanthemum （TFCC） and the large conductance Ca²⁺- activated K⁺ （BK_Ca） channels on vascular smooth muscle cells （VSMCs） of the middle cerebral artery in rats. In addition， this study will also investigate the effect of TFCC on the expression of BK_Ca channel alpha protein in rat middle cerebral artery VSMCs. MethodsThe primary method employed was acute digestion to isolate VSMCs from the middle cerebral artery of rats； whole-cell patch-clamp techniques were used to measure BK_Ca channel currents； primary tissue adherence culture was utilized to cultivate VSMCs from the middle cerebral artery of rats； Western blot were employed to determine protein expression levels. ResultsIn whole-cell patch-clamp experiments， both the H₂S donor NaHS （100 μmol/L） and endogenous H₂S enhanced BK_Ca channel currents. TFCC （30， 90， and 270 mg/L） also activatedBK_Ca channels and exhibited a certain concentration-dependent effect. Even after blocking endogenous H₂S production， TFCC （270 mg/L） still activated BK_Ca channels in VSMCs of the middle cerebral artery in rats. In Western blot experiments， the α-subunit of BK_Ca channel proteins was expressed in all groups of cells， but TFCC （30， 90， and 270 mg/L） and inhibitor IBTX group did not affect the expression of channel protein content.Conclusion TFCC can promote the opening of BK_Ca channels by promoting the generation of endogenous H₂S， or directly activate BK_Ca channels， thereby playing a role in relaxing cerebral blood vessels. However， TFCC had no significant effect on the expression of BK_Ca channel proteins.

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.

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.

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.

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.

Objective:To analyze the values of platelet transforming growth factor-β (TGF-β) and SMAD family member 2 (Smad2) in patients′ peripheral platelets for CRC diagnosis and staging.Methods:Retrospective case-control study. Tumor tissues, paratumor tissues and peripheral blood samples were collected from 248 CRC patients (147 males, 101 females; age 21-93 years) diagnosed in the First Hospital of Jilin University from October 10th, 2020, to March 10th, 2025. Peripheral blood samples were also collected from 40 colorectal adenomatous polyp patients (21 males, 19 females; age 22-74 years) and 75 healthy individuals (43 males, 32 females; age 18-81 years) during the same period. Tissue homogenates and platelets were isolated using tissue disruption and gradient centrifugation, respectively. Total RNA was respectively extracted from tissues and platelets, and the expression levels of TGF-β and Smad2 were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) expressed as relative quantity 2 -ΔΔCt. Differences of TGF-β and Smad2 expression were compared between CRC tissues and adjacent tissues, as well as among CRC patients, polyp patients, and healthy controls. The relationship of platelet TGF-β and Smad2 expression with pathological features includingtumor stage, pathological type, and metastasis were analyzed. The efficiency of platelet TGF-β, Smad2, and their combination in diagnosing CRC was evaluated using receiver operating characteristic (ROC) curves. Results:The expression levels of TGF-β and Smad2 in CRC tumor tissues[1.09 (0.45, 2.00), 2.93 (0.78, 6.73)] were significantly higher than those in adjacent tissues[0.81 (0.27, 1.50), 1.29 (0.40, 2.63)] ( Z TGF-β=4.54, Z Smad2=6.67, both P<0.001). The expression levels of TGF-β and Smad2 in platelets of CRC patients[2.73(1.53, 4.38), 3.16 (1.58, 4.38)] were significantly higher than those in the colorectal polyp group[1.23(0.70, 2.54), 1.16(0.78, 2.27)] and the healthy control group[0.96(0.51, 1.88), 0.92 (0.55, 1.88)] ( H TGF-β=59.71, H Smad2=78.74, both P<0.001). Platelet TGF-β expression increased progressively with tumor stage (stage 1-4) ( P<0.05), while platelet Smad2 levels were higher in metastatic CRC compared with non-metastatic cases ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) for diagnosing CRC when combining platelet TGF-β and Smad2 was 0.81[95%Confidence interval( CI) 0.77—0.86], which was 0.90 (95% CI 0.86—0.93) if adding serum carcinoembryonic antigen (CEA). Conclusion:Platelet TGF-β and Smad2 expression correlates with the diagnosis and staging of CRC, demonstrating potential as liquid biopsy biomarkers for colorectal malignancies.

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 analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.

Objective To establish a ultrahigh-performance liquid chromatography-orbitrap high-resolution mass spectrometry(UHPLC-Orbitrap HRMS)method for the determination of the genotoxic impurity N-nitroso propranolol(NPPN)in propranolol hydrochloride sustained-release tablets.Methods The test sample was ultrasonically extracted using methanol as the solvent,then centrifuged and filtered before injection analysis.Chromatographic separation was performed using a 2.7 μm particle size C18 UHPLC column with a mobile phase of 0.1％formic acid(A)in water and 0.1％formic acid(B)in acetonitrile,using gradient elution.Mass spectrometry was conducted with an HESI ion source in positive ion parallel reaction monitoring(PRM)scan mode,monitoring the NPPN fragment ion at m/z 72.080 8,and quantification was performed using the standard curve method.Results The calibration curve was in good linearity in the range of 0.51-20.30 ng·mL-1 with excellent correlation coefficient(r)of 0.9999.The recoveries of NPPN at three levels(low,medium,and high)were in the range of 95.4％～98.3％,while the RSDs were from 2.5％to 4.2％.The limit of detection(LOD)was 0.20 ng·mL-1 while the limit of quantitfication(LOQ)was 0.51 ng·mL-1.This analytical method was used to determine NPPN in six batches of propranolol hydrochloride sustained release tablet samples.NPPN was detected in all six samples,among which the detection amount of 3 batches have exceeded the acceptable limit.Conclusion This method is sensitive,accurate,and fast,making it useful for pharmaceutical companies in controlling production processes and providing robust technical support for regulatory authorities.

Objective To investigate the oral health status of second-grade primary school students in Suzhou,provide baseline data for evaluating Suzhou's"Bright Eyes and Healthy Teeth"public health project,and offer reference for formulating oral health policies for students in Suzhou.Methods A multi-stage,stratified,random sampling method was used to select 1 640 second-grade primary school students from 10 districts(county-level cities)across Suzhou.The oral health survey of primary school students in Suzhou was designedbased on WHO"Basic Methods for Oral Health Surveys"(5th edition).A survey on the students' oral health status was con-ducted.Results The caries prevalence,mean DMFT(Decayed,Missing,Filled Teeth),and caries filling rate for primary teeth among second-grade students in Suzhou were 80.73％,4.25,and 24.48％,respectively.For permanent teeth,the caries prevalence,mean DMFT(Decayed,Missing,Filled Teeth),and caries filling rate were 30.30％,0.62,and 16.96％,respectively.Specifically,the caries prevalence,mean DMFT,and filling rate for the first permanent molar were 29.88％,0.59,and 16.94％,respectively.The pit and fissure sealing rate for the first permanent molar was 13.74％.Additionally,the detection rate for gingival bleeding was 58.05％,and for dental calculus,49.15％.Conclusion The oral health status of second-grade primary school students in Suzhou is concerning.The caries prevalence rate for both primary and permanent teeth is high,while the filling rate is relatively low.Prior to the implementation of oral health programs,the pit and fissure sealing rate for the first permanent molars was low,with significant differ-ences observed between urban and rural areas,as well as among different districts(or county-level cities).