Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Risks of food safety induced by small molecule drug residues in animal food and environment have become an increasing public concern,so it is necessary to develop highly sensitive and easy-to-operate techniques to detect small molecules.Herein,a metasurface plasma resonance(MetaSPR)sensor chip coupled with gold nanoparticles(AuNPs)was developed for detection of enrofloxacin(ENR)based on competitive immunoassay.The detection range of the sensor for ENR was 0.025-3.2 ng/mL,and the detection limit(3σ)was 20 pg/mL.The biosensor showed excellent performance including high selectivity,good stability,ease to operate and high throughput,etc.The developed method was applied to detection of ENR residues in real samples,with recoveies of 96.0% -105.0%.The proposed sensing strategy provided new technique reference for detection of other small molecules in the field of residue analysis in food safety and environment monitoring.

Objective:To investigate the influence of the complexity metrics of the multi-leaf collimator (MLC) on the γ-pass rate of volumetric modulated arc therapy (VMAT) plans for nasopharyngeal carcinoma (NPC).Methods:A total of 60 VMAT plans for NPC were selected to measure the γ-pass rate. The MLC data across all control points (CPs) in each VMAT plan were analyzed to calculate the mean field area (MFA), average leaf gap (ALG), small aperture score (SAS), and their corresponding weighted metrics including MFAW, ALGW, and SASW, considering dose weight (W). Pearson′s bivariate correlation analysis was conducted to examine the correlations between MLC complexity metrics and the γ-pass rate. Moreover, the receiver operating characteristic (ROC) analysis was employed to assess the predictive efficacy of MLC complexity metrics on dose verification result.Results:Under the 3%/3 mm, 3%/2 mm, and 2%/2 mm criteria, the MFA in the 60 VMAT plans exhibited a positive correlation with the γ-pass rate ( r=0.82, 0.79, 0.72, P<0.05), and the MFAW was also positively correlated with the γ-pass rate ( r=0.83, 0.81, 0.75, P<0.05). The ALG manifested a positive correlation with the γ-pass rate ( r=0.82, 0.79, 0.74, P<0.05), as did the ALGW ( r=0.83, 0.81, 0.77, P<0.05). The SAS(0-1 cm), SAS(1-2 cm), SAS(2-3 cm), and SAS(3-4 cm) displayed negative correlations with the γ-pass rate ( r= -0.86, -0.82, -0.71, -0.84, -0.82, -0.72, -0.79, -0.79, -0.73, -0.30, -0.35, -0.42, P<0.05), whereas the SAS(4-5 cm), SAS(5-6 cm), and SAS(6-40 cm) showed positive correlations with the γ-pass rate ( r=0.49, 0.45, 0.33, 0.73, 0.71, 0.59, 0.79, 0.79, 0.76, P<0.05). The outcomes of SASW reveal slightly stronger correlations than those of SAS. In terms of correlations among complexity metrics, a positive correlation was observed between MFA and ALG ( r=0.98, P<0.05). ALG was negatively correlated with SAS(0-1 cm), SAS(1-2 cm), SAS(2-3 cm), and SAS(3-4 cm) ( r= -0.95, -0.94, -0.89, -0.39, P<0.05), and positively correlated with SAS(4-5 cm), SAS(5-6 cm), and SAS(6-40 cm) ( r=0.51, 0.77, 0.92, P<0.05). The weighted result mirrored these correlations. The ROC-derived analytical result indicate that MFA, MFAW, ALG, ALGW, SAS(0-1 cm), SAS(1-2 cm), SAS(2-3 cm), SAS(6-40 cm), SASW(0-1 cm), SASW(1-2 cm), SASW(2-3 cm), and SASW(6-40 cm) demonstrated exceptional predictive efficacy for dose verification result [Area under the curve (AUC) > 0.9, P<0.05]. Conclusions:The γ-pass rate of VMAT plans for NPC is strongly correlated with MLC complexity metrics, which demonstrate excellent predictive efficacy for dose verification result. The increased uncertainty in dose calculations and measurements caused by narrow fields generated by the MLC is a significant factor contributing to the reduced γ-pass rate of VMAT plans. This finding is associated with discrepancies in the precision of treatment planning system (TPS) modeling and the accuracy of dose verification tools, providing a reference for similar challenges.

Objective:To investigate the differences in dosimetric parameters for target volumes and organs at risk (OARs), radiation doses to reconstructed tissues, and beam-on time in radiotherapy among helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (F_IMRT) following immediate breast reconstruction for breast cancer, thereby providing a reference for the selection of clinical radiotherapy techniques.Methods:This study retrospectively investigated 15 breast cancer patients who underwent radiotherapy following modified radical mastectomy and immediate breast reconstruction at the Liuzhou Worker′s Hospital from August 2018 to July 2023. During target volume delineation, precautions were taken to avoid the reconstructed tissues, which were delineated separately. Customized HT, VMAT, and F_IMRT treatment plans were designed for each patient. The plans were categorized into the HT, VMAT, and F_IMRT groups based on different radiotherapy techniques employed. They were comparatively analyzed through one-way analysis of variance (ANOVA), with multiple comparisons further conducted in the case of significant differences.Results:Statistical analyses reveal significant differences in various parameters of target volumes among the three groups of plans ( F = 38.73, 14.95, 37.01, 48.05, 35.55, 22.56, 34.30, P < 0.05). Pairwise comparisons indicate that the maximum dose ( D2%), minimum dose ( D98%), mean dose ( Dmean), and the proportion of high-dose volumes within the target volume ( V107%and V110%) in both the HT and VMAT groups were significantly better than those in the F_IMRT group. The HT group demonstrated the optimal conformity index (CI), while the VMAT group displayed the superior homogeneity index (HI) compared to the other two groups. In terms of OAR, the V20 of the ipsilateral lung was the lowest in the HT group ( F = 14.31, P < 0.05) and the highest in the F_IMRT group ( F = 14.31, P < 0.05). However, the V5 and Dmean for both the ipsilateral and contralateral lungs in the HT group significantly surpassed those of the other groups ( F = 39.16, 31.91, P < 0.05). The mean dose Dmean ( F = 5.57, P < 0.05) of the contralateral breast was significantly reduced in the VMAT group compared to the other two groups. No statistically significant differences were observed for other OARs, including the heart, spinal cord PRV, thyroid, and humeral head ( P > 0.05). The radiation doses to reconstructed tissues ( Dmax, V53.5, Dmean) ascended in the order of HT, VMAT, and F_IMRT groups ( F = 17.69, 17.53, 15.11, P < 0.05). The HT and F_IMRT groups showed similar beam-on times ( P > 0.05), both exceeding that of the VMAT group by several folds ( F = 28.72, P < 0.05). Conclusions:The comparative analysis indicates that the three radiotherapy techniques exhibit distinct advantages and limitations, with F_IMRT demonstrating the least comprehensive advantage. HT can enhance the conformity of target volumes while reducing the overall radiation doses to reconstructed tissues and the crucial indicator V20 in the ipsilateral lung. VMAT demonstrates the highest treatment efficiency, yielding improved dose uniformity in the target volume and reduced radiation doses to the contralateral breast. It is advisable to prioritize HT or VMAT based on actual clinical conditions.

This paper reported a case of fetal congenital chloride diarrhea (CCD) indicated by prenatal ultrasound and confirmed by whole-exome sequencing. At 26 weeks and two days of gestation, a routine prenatal ultrasound revealed fetal bowel dilation and numerous floating echogenic particles in the amniotic fluid, suggesting the possibility of CCD. Multiple follow-up ultrasounds in late pregnancy showed persistent bowel dilation, polyhydramnios with numerous floating echogenic particles, and fetal development larger than the gestational age. Whole-exome sequencing and Sanger validation revealed two compound heterozygous mutations in the fetal SLC26A3 gene: c.2006C>A (p.S669*) inherited from the mother and c.1355T>A (p.L452Q) inherited from the father, leading to a diagnosis of CCD. Postnatally, the infant exhibited persistent watery diarrhea. Based on prenatal ultrasound and diagnostic results, the infant was immediately given intravenous and oral electrolyte supplementation after birth, preventing severe electrolyte imbalance. As of June 2024, the infant was five months old, with follow-up showing good growth and development.

Objective:To explore the safety of laparoscopic modified transcystic biliary drainage(modified C-tube technique)in the treatment of biliary stones and application of diagnosing biliary disease.Methods:A retrospective analysis was conducted on the clinical data of 68 cases of biliary stones successfully treated with laparoscopic modified C-tube technique from August 2021 to December 2023.The safety,effectiveness,and area of applications were analyzed.The reliability of the principle of the modified fixation method was verified by using an ex vivo gallbladder.Results:Three cases of ex vivo gallbladder demonstrated that the strength of the modified fixation method was reliable,and the sinus tract formed by suture after immediate extraction of the C tube could be dislocated and closed,resisting the bile outflow caused by the weight of the gallbladder.Among the 68 patients,42 were difficult biliary stones,6 were suspected common bile duct stones,and 5 were extrahepatic bile duct stones combined with intrahepatic bile duct stones.Among them,48 cases underwent choledochoscopy assisted trans-choledochal approach for stone removal,and 10 cases underwent transcystic approach stone removal,Six patients underwent simply basket exploration and removal of stones through the cystic duct(5 patients had no residual stones on postoperative C-tube angiography,1 patient had suspected residual stones,and the patient refused further examination and treatment for no symptom),and 4 patients only underwent biliary drainage through the cystic duct;two patients with retained stone passed after the use of topical nitrate drip infusion via C-tube,seven cases underwent endoscopic retrograde cholangiopancreatography(ERCP),stone removal with the assistance of a C-tube after laparoscopic surgery,and the results were uneventful.The mean surgical time was(131±44)min(76-279 min),the maximum daily drainage volume of the C-tube was(401±235)mL/d(10-1 150 mL/d),the hospital stay was(8.6±3.6)d(2-19 d),and the mean time of C-tube removal was(11±6.9)d(5-46 d).There were 14 overall complications,including 2 residual stones,and 12 C-tube related complications,comprising of 1 gradeⅢ a,2 grade Ⅱ,and 9 grade Ⅰ.There were 9 cases of C-tube related adverse events that did not cause complications,including 3 of early detachment,2 of displacement,and 4 of deep insertion.The median follow-up time after surgery was 21(2-30)months,and 5 patients had recurrent stones.Among them,4 patients had slow contrast outflow during cholangiogram,and 1 patient had obvious pancreaticobiliary reflux.55 patients underwent C-tube amylase measurement,and 9 cases showed a significant increase in bile amylase(349-44 936 U/L),suggesting the presence of pancreaticobiliary reflux.Conclusion:Laparoscopic modified C-tube technique can be effectively used in the treatment of biliary stones,which is relatively safe and can be attempted in the diagnosis of biliary diseases.

In recent years, the application of artificial intelligence (AI) in the field of biology has witnessed remarkable advancements. Among these, the most notable achievements have emerged in the domain of protein structure prediction and design, with AlphaFold and related innovations earning the 2024 Nobel Prize in Chemistry. These breakthroughs have transformed our ability to understand protein folding and molecular interactions, marking a pivotal milestone in computational biology. Looking ahead, it is foreseeable that the accurate prediction of various physicochemical properties of proteins—beyond static structure—will become the next critical frontier in this rapidly evolving field. One of the most important protein properties is thermodynamic stability, which refers to a protein’s ability to maintain its native conformation under physiological or stress conditions. Accurate prediction of protein stability, especially upon single-point mutations, plays a vital role in numerous scientific and industrial domains. These include understanding the molecular basis of disease, rational drug design, development of therapeutic proteins, design of more robust industrial enzymes, and engineering of biosensors. Consequently, the ability to reliably forecast the stability changes caused by mutations has broad and transformative implications across biomedical and biotechnological applications. Historically, protein stability was assessed via experimental methods such as differential scanning calorimetry (DSC) and circular dichroism (CD), which, while precise, are time-consuming and resource-intensive. This prompted the development of computational approaches, including empirical energy functions and physics-based simulations. However, these traditional models often fall short in capturing the complex, high-dimensional nature of protein conformational landscapes and mutational effects. Recent advances in machine learning (ML) have significantly improved predictive performance in this area. Early ML models used handcrafted features derived from sequence and structure, whereas modern deep learning models leverage massive datasets and learn representations directly from data. Deep neural networks (DNNs), graph neural networks (GNNs), and attention-based architectures such as transformers have shown particular promise. GNNs, in particular, excel at modeling spatial and topological relationships in molecular structures, making them well-suited for protein modeling tasks. Furthermore, attention mechanisms enable models to dynamically weigh the contribution of specific residues or regions, capturing long-range interactions and allosteric effects. Nevertheless, several key challenges remain. These include the imbalance and scarcity of high-quality experimental datasets, particularly for rare or functionally significant mutations, which can lead to biased or overfitted models. Additionally, the inherently dynamic nature of proteins—their conformational flexibility and context-dependent behavior—is difficult to encode in static structural representations. Current models often rely on a single structure or average conformation, which may overlook important aspects of stability modulation. Efforts are ongoing to incorporate multi-conformational ensembles, molecular dynamics simulations, and physics-informed learning frameworks into predictive models. This paper presents a comprehensive review of the evolution of protein thermodynamic stability prediction techniques, with emphasis on the recent progress enabled by machine learning. It highlights representative datasets, modeling strategies, evaluation benchmarks, and the integration of structural and biochemical features. The aim is to provide researchers with a structured and up-to-date reference, guiding the development of more robust, generalizable, and interpretable models for predicting protein stability changes upon mutation. As the field moves forward, the synergy between data-driven AI methods and domain-specific biological knowledge will be key to unlocking deeper understanding and broader applications of protein engineering.

Objective To observe the efficacy of self-made auxiliary reduction device combined with sinus tarsi approach(STA)in the treatment of Sanders type Ⅱ to Ⅳ calcaneal fractures.Methods A total of 40 patients with Sanders type Ⅱ to Ⅳ calcaneal fractures admitted to our hospital from January to June 2023 were selected and divided into the control group and the observation group by the random number table method,with 20 cases in each group.Patients in the control group underwent surgical treatment with the heel extensile lateral approach(ELA),while patients in the observation group underwent surgical treatment with the auxiliary reduction device combined with STA.The surgical-related indicators,postoperative complications and ankle-foot anatomical indicators of patients in the two groups were compared.The recovery of limb function was evaluated by the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scale and Maryland foot function score.Results There was no statistically significant difference in the operation time,postoperative incision drying time,or duration of postoperative pain between the two groups(P>0.05).The postoperative suture removal time of the patients in the observation group was shorter than that of the control group,and the difference was statistically significant(P<0.05).The incidence of skin edge necrosis of incision and the total incidence of complications of patients in the observation group were significantly lower than those in the control group(P<0.05).The B?hler angle and Gissane angle of patients in both groups increased after surgery compared with those before surgery(P<0.05);there was no statistically significant difference in the B?hler angle or Gissane angle after surgery of patients between the two groups(P>0.05).The AOFAS score1 week after surgery of the patients in the observation group was higher than that in the control group(P<0.05),while there were no statistically significant differences in the AOFAS scores or Maryland scores of patients at other time points between the two groups(P>0.05).Conclusion The use of the auxiliary reduction device in surgical treatment with STA for Sanders type Ⅱ to Ⅳ calcaneal fractures can effectively restore the function of the foot and ankle,with short postoperative suture removal time and low incidence of postoperative complications.

Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00％～125.00％.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.

Objective:A GC method was established for the determination of three potential genotoxic impuri-ties methyl ethanesulfonate,ethyl ethanesulfonate and isopropyl ethanesulfonate in baritinib raw materials.Methods:The chromatography was performed on Agilent J&W DB-1701(30 m×0.25 mm,1.0 μm)col-umn.The heating procedure was the initial temperature of 100℃,maintained for 3 min,at the rate of 5℃per minute to 180℃,maintained for 2 min,and then at the rate of 30℃per minute to 240℃,maintained for 5 min.The temperature of the injector was 240℃.The shunt ratio was 1∶10.The carrier gas was helium with a flow rate of 2.0 mL per minute.The temperature of the detector was 260℃and the injection volume was 2 μL.Results:The specificity,linearity and range,limit of quantification and detection,accuracy,pre-cision,repeatability and stability of the method meet the requirements.Conclusion:The analytical method is simple,accurate,sensitive and reproducible,and can be used for quality control of three potential genotoxic impurities in baritinib.