Organ transplantation is an effective treatment for end-stage organ failure, but postoperative infections and rejection reactions are key factors affecting the survival of the patients. Recently, the incidence of human parvovirus B19 (B19V) infection following transplantation has increased. B19V is a non-enveloped virus that primarily infects the upper respiratory tract and exhibits significant tropism for erythroid progenitor cells in the bone marrow, leading to the lysis of erythrocytes and hematological abnormalities. After B19V viremia, it may further infect other cells, triggering inflammatory responses and tissue damage. B19V infection may lead to chronic anemia in organ transplant patients, thereby affecting the success of the transplant and the survival of the patients. Therefore, it is essential to diagnose and monitor B19V infection post-transplantation. Due to the immunosuppressive therapy following transplantation, traditional serological detection methods, such as IgM and IgG antibody tests, are often unreliable. In contrast, molecular biological detection, especially real-time fluorescent quantitative PCR technology, provides more accurate results. However, the diversity of B19V genotypes may lead to the missed detection of some genotypes. Thus, it is necessary to use different detection techniques to improve the diagnostic accuracy of B19 virus infections. Additionally, there is a need to explore more precise diagnostic methods to enhance the early identification and management of B19V infection, further improving the survival and life quality of the patients.

AIM To investigate the clinical effects of Huoxue Qingre Formula combined with radiofrequency ablation on patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis.METHODS Ninety patients were randomly assigned into control group(45 cases)for 3-month intervention of both Huoxue Qingre Formula placebo and radiofrequency ablation,and observation group(45 cases)for 3-month intervention of both Huoxue Qingre Formula and radiofrequency ablation.The changes in clinical effects,VRR,TCM syndrome score,cytokines(TNF-α,IFN-γ,IL-23,IL-1β),biochemical indices[Ca2+,25(OH)D,CRP],thyroid function indices(TSH,FT3,FT4)and safety indices were detected.RESULTS At postoperative 12 months,the observation group demonstrated higher total effective rate than the control group(P＜0.05).At postoperative 3-12 months,the two groups displayed increased VRR(P＜0.05),especially for the observation group(P＜0.05,P＜0.01).At the 7th,30th postoperative days,the two groups displayed decreased TCM syndrome score and cytokines(P＜0.05,P＜0.01),especially for the observation group(P＜0.05,P＜0.01).At the 30th postoperative day,the two groups displayed decreased Ca2+(P＜0.01)and increased 25(OH)D(P＜0.01),especially for the observation group(P＜0.01).At the 7th postoperative day,the two groups displayed increased CRP(P＜0.01),especially for the control group(P＜0.05),which were decreased at the 30th postoperative day(P＜0.05,P＜0.01),especially for the observation group(P＜0.01).No significant differences in thyroid function indices and safety indices were found between the two groups(P＞0.05).CONCLUSION For the patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis,Huoxue Qingre Formula combined with radiofrequency ablation can safely and effectively enhance nodule VRR,alleviate discomfort symptoms,reduce TCM syndrome score,inflammatory factor levels,and accelerate recovery.

Bismuth iodide(BiOI)with different crystal plane ratios of(110)to(001)was synthesized,and typeⅡheterojunction formed between(001)and(110)crystal planes of BiOI was used to improve the separation efficiency of photogenerated electrons and holes.Then the BiOI(001)/(110)was composited with nitrogen-doped graphene quantum dots(N-GQDs)to prepare a ternary composites,which could enhance the range and intensity of light absorption,and prolonged the lifetime of photogenerated electrons due to the formation of Z-scheme heterojunctions between BiOI and N-GQDs,thereby leading to the excellent photoelectric performance of the BiOI/N-GQDs for generating sensitive photoelectric response signals.A photoelectrochemical sensor for sensitive detection of chlorpyrifos(CPF)was designed with BiOI/N-GQDs-modified FTO electrode as a photocathode.The S and N atoms contained in CPF were coordinated with Bi(Ⅲ)on the surface of BiOI,which reduced the photocurrent of BiOI/N-GQDs.The photocurrent change was linear with logarithm of concentration of CPF in the range of 1.5×10-12-5.0×10-9 mol/L,and the detection limit was 1.5×10-12 mol/L.The sensor was highly sensitive,selective and stable,and could be used for determination of trace CPF in environmental and food samples.

Objective To explore a deep learning-based automatic bone age estimation model for elbow joint X-ray images of Chinese Han adolescents and children and evaluate its performance.Methods A total of 943(517 males and 426 females)elbow joint frontal view X-ray images of Chinese Han ado-lescents and children aged 6.00 to<16.00 years were collected from East,South,Central and North-west China.Three experimental schemes were adopted for bone age estimation.Scheme 1:Directly in-put preprocessed images into the regression model;Scheme 2:Train a segmentation network using"key elbow joint bone annotations"as labels,then input segmented images into the regression model;Scheme 3:Train a segmentation network using"full elbow joint bone annotations"as labels,then in-put segmented images into the regression model.For segmentation,the optimal model was selected from U-Net,UNet++and TransUNet.For regression,VGG16,VGG19,InceptionV2,InceptionV3,ResNet34,ResNet50,ResNet101 and DenseNet121 models were selected for bone age estimation.The dataset was randomly split into 80%(754 samples)for training and validation for model fitting and hyperparameter tuning,and 20%(189 samples)as an internal test set to test the performance of the trained model.An additional 104 elbow joint X-ray images from the same demographic and age group were col-lected and used as an external test set.Model performance was evaluated by comparing the mean ab-solute error(MAE),root mean square error(RMSE),accuracies within±0.7 years(P±0.7 years)and±1.0 years(P±1.0 years)between the estimated age and the actual age,and by drawing radar charts,scat-ter plots,and heatmaps.Results When segmented with Scheme 3,the UNet++model achieved good segmentation performance with a segmentation loss of 0.000 4 and an accuracy of 93.8%at a learning rate of 0.000 1.In the internal test set,the DenseNet121 model with Scheme 3 yielded the best results with MAE,P±0.7 years and P±1.0 years being 0.83 years,70.03%,and 84.30%,respectively.In the external test set,the DenseNet121 model with Scheme 3 also performed best,with an average MAE of 0.89 years and an average RMSE of 1.00 years.Conclusion When performing automatic bone age estima-tion using elbow joint X-ray images in Chinese Han adolescents and children,it is recommended to use the UNet++model for segmentation.The DenseNet121 model with Scheme 3 achieves optimal per-formance.Using segmentation networks,especially that trained with annotation areas encompassing the full elbow joint including the distal humerus,proximal radius,and proximal ulna,can improve the ac-curacy of bone age estimation based on elbow joint X-ray images.

Objective To explore a deep learning network model suitable for bone age estimation using shoulder joint X-ray images in Chinese Han adolescents.Methods A retrospective collection of 1 286 shoulder joint X-ray images of Chinese Han adolescents aged 12.0 to<18.0 years(708 males and 578 females)was conducted.Using random sampling,approximately 80%of the samples(1 032 cases)were selected as the training and validation sets for model learning,selection and optimization,and the other 20%samples(254 cases)were used as the test set to evaluate the model's generalization ability.The original single-channel shoulder joint X-ray images and dual-channel inputs combining original images with segmentation labels(manually annotated shoulder joint regions multiplied pixel-by-pixel with original images,followed by segmentation via the U-Net++network to retain only key shoulder joint region information)were respectively input into four network models,namely VGG16,ResNet18,ResNet50 and DenseNet121 for bone age estimation.Additionally,manual bone age estimation was con-ducted on the test set data,and the results were compared with the four network models.The mean absolute error(MAE),root mean square error(RMSE),coefficient of determination(R2),and Pear-son correlation coefficient(PCC)were used as main evaluation indicators.Results In the test set,the bone age estimation results of the four models with dual-channel input of shoulder joint X-ray images outperformed those with single-channel input in all four evaluation indicators.Among them,DenseNet121 with dual-channel input achieved best results with MAE of 0.54 years,RMSE of 0.82 years,R2 of 0.76,and PCC(r)of 0.88.Manual estimation yielded an MAE of 0.82 years,ranking second only to dual-channel DenseNet121.Conclusion The DenseNet121 model with dual-channel input combined with original images and segmentation labels is superior to manual evaluation results,and can effectively estimate the bone age of Chinese Han adolescents.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Aim To investigate the mechanism by which Aiweixin oral liquid(AWX)alleviates myocar-dial ischemia-reperfusion injury in rats through the reg-ulation of mitochondrial fusion and fission.Methods Seventy-two healthy male Sprague-Dawley rats were randomly assigned to six groups(n=12)using a ran-dom number table:sham surgery group,model group,low-dose AWX(1 mL·kg-1)group,medium-dose AWX(2 mL·kg-1)group,high-dose AWX(4 mL·kg-1)group,and positive control drug trimetazidine(10 mg·kg-1)group.A myocardial ischemia-reper-fusion injury(MIRI)model was established by ligating the left anterior descending coronary artery of the rat heart,followed by 30 minutes of ischemia and 90 mi-nutes of reperfusion.In the sham surgery group,only a suture was placed without ligation.The rats in the treatment groups were pre-gavaged with AWX starting 10 days prior to the modeling procedure.Lead Ⅱ elec-trocardiograms were recorded before and after reperfu-sion in each group to observe the changes in electrocar-diographic parameters.The myocardial infarct size in each group was assessed using TTC staining.The his-topathological changes in myocardial tissue were exam-ined under a light microscope using hematoxylin and eosin(HE)staining.The serum levels of adenosine triphosphate(ATP)and cardiac troponin I(cTnI)were measured using enzyme-linked immunosorbent as-say(ELISA).Superoxide dismutase(SOD)activity and the levels of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were determined using bio-chemical assay kits.The protein expression levels of dynamin-related protein 1(dynamin-relatedprotein 1,DRP1),mitochondrial fission factor(mitochondrial fis-sion factor,MFF),mitochondrial fission protein 1(mi-tochondrial fission protein 1,FIS1),mitofusin 1(mito-fusion-1,MFN1),and mitofusin 2(mitofusion-2,MFN2)were evaluated by Western blot analysis.Re-sults Compared with the sham group,the model group exhibited aggravated myocardial tissue pathological damage,an increased percentage of myocardial infarct size,decreased serum SOD activity and ATP levels,and significantly elevated levels of MDA,cTnI,and LDH activity.Additionally,the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1 was up-regulated,while the expression of fusion-related factors MFN1 and MFN2 was downregulated.Compared with the model group,Aiweixin oral liquid significantly alle-viated myocardial injury,reduced the percentage of my-ocardial infarct size,increased serum SOD activity and ATP levels,decreased MDA content and cTnI and LDH activity,downregulated the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1,and up-regulated the protein expression of fusion-related factors MFN1 and MFN2.Conclusion Aiweixin oral liquid alleviates myocardial ischemia-reperfusion injury in rats by regulating abnormal mitochondrial fusion and fis-sion.

Objective To carry out emergency medical system modification design for EC135 P3H helicopter without compromising the original airframe structure so as to enhance aeromedical rescue capabilities.Methods Firstly,the original cabin seats were removed and medical floor was installed in the cabin;secondly,the medical chair,medical stretcher trolley and its fixing components,storage boxes and oxygen cylinders were mounted onto the floor;finally,a medical equipment fixing frame was formed based on the original helicopter sill structure so as to accommodate medical devices such as defibrillators,ventilators and injection pumps.The modification design scheme had its effectiveness verified with overall aircraft load balance analysis,mechanical analysis,dynamic impact tests of seats and actual modification and flight tests.Results EC135 P3H helicopter proved to meet all the airworthiness certification requirements after emergency medical system modification.Conclusion The proposed modification scheme enables EC135 P3H helicopter to rapidly transition between standard and medical configurations,enhancing its emergency medical rescue capabilities and providing references for medical modifications of helicopters with similar configurations.

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

OBJECTIVE: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional