Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

OBJECTIVE: To investigate the effectiveness of using 3 hollow compression screws combined with 1 screw off-axis fixation under the guidance of three-dimensional (3D) printed guide plate with mortise-tenon joint structure (mortise-tenon joint plate) for the treatment of Pauwels type Ⅲ femoral neck fractures. METHODS: A clinical data of 78 patients with Pauwels type Ⅲ femoral neck fractures, who were admitted between August 2022 and August 2023 and met the selection criteria, was retrospectively analyzed. The operations were assisted with mortise-tenon joint plates in 26 cases (mortise-tenon joint plate group) and traditional guide plates in 28 cases (traditional plate group), and without guide plates in 24 cases (control group). There was no significant difference in the baseline data of gender, age, body mass index, cause of injury, and fracture side between groups ( P>0.05). The operation time, intraoperative blood loss, frequency of intraoperative fluoroscopy, incision length, incidence of postoperative deep vein thrombosis of lower extremity, pain visual analogue scale (VAS) score at 1 week after operation, and Harris score of hip joint at 3 months after operation were recorded and compared. X-ray re-examination was taken to check the quality of fracture reduction, fracture healing, and the shortening length of the femoral neck at 3 months after operation, and the incidences of internal fixation failure and osteonecrosis of the femoral head during operation. RESULTS: Compared with the control group, the operation time, intraoperative blood loss, and frequency of intraoperative fluoroscopy reduced in the two plate groups, and the quality of fracture reduction was better, but the incision was longer, and the differences were significant ( P<0.05). The operation time and intraoperative blood loss were significantly higher in the traditional plate group than in the mortise-tenon joint plate group ( P<0.05), the incision was significantly longer ( P<0.05); and the difference in fracture reduction quality and the frequency of intraoperative fluoroscopy was not significant between two plate groups ( P>0.05). There was 1 case of deep vein thrombosis of lower extremity in the traditional plate group and 1 case in the control group, while there was no thrombosis in the mortise-tenon joint plate group. There was no significant difference in the incidence between groups ( P>0.05). All patients were followed up 12-15 months (mean, 13 months). There was no significant difference in VAS score at 1 week and Harris score at 3 months between groups ( P>0.05). Compared with the control group, the fracture healing time and the length of femoral neck shortening at 3 months after operation were significantly shorter in the two plate groups ( P<0.05). There was no significant difference between the two plate groups ( P>0.05). There was no significant difference in the incidences of non-union fractures, osteonecrosis of the femoral head, or internal fixation failure between groups ( P>0.05). CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the use of 3D printed guide plate assisted reduction and fixation can shorten the fracture healing time, reduce the incidence of postoperative complications, and be more conducive to the early functional exercise of the affected limb. Compared with the traditional guide plate, the mortise-tenon joint plate can reduce the intraoperative bleeding and shorten the operation time.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Bone Screws ; Adult ; Aged ; Treatment Outcome ; Printing, Three-Dimensional ; Operative Time

Objective: To explore the mechanism of action of Zangjiangzhi capsule (ZJZC) in treating hyperlipidemia (HLP). Methods: The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS/MS). Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment. The SwissTargetPrediction database was used to predict compound targets, and GeneCards, DisGeNet, OMIM, and DRUGBANK databases were used to identify HLP-related targets. Protein–protein interaction diagrams were constructed using the STRING database. The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The “herb-ingredient-target” network was visualized using Cytoscape. Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay. Results: Ninety compounds were identified in ZJZC, including 34 flavonoids, 12 phenols, 10 terpenoids, 10 alkaloids, 8 organic acids, 8 anthraquinones, and 9 other compounds. In total, 904 targets were identified for these compounds. Among them, 158 targets intersected with the HLP target network. Network pharmacology analysis showed that MAPK1, PPAR-α, RXRA, HSP90AA1, PIK3R1, AKT1, PIK3CA, IL6, TNF, and ESR1 are the key targets of action. KEGG enrichment analysis identified 164 pathways. Among these, the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis pathways, regulation of lipids in adipocytes, and insulin resistance are related to HLP. Molecular docking showed good affinity between the key targets and ingredients. Further, ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-α protein, which have been shown to be strongly associated with HLP. Conclusions This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP, providing evidence at the molecular level for its clinical application in the treatment of HLP.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective To address the difficulty in collecting sufficient endoscopic images of colorectal submucosal tumors for traditional deep learning model training,a few-shot learning based model(FSL model)is proposed for classifying colorectal submucosal tumors and polyps on endoscopic images.Methods A total of 172 endoscopic images of colorectal submucosal tumors were collected from different centers,including 43 each of colorectal lipomas(CRLs),neuroendocrine tumors(NETs),serrated lesions and polyps(SLPs),and traditional adenomas.A support set and a query set were constructed using these endoscopic images.ResNet50 which was pre-trained on ImageNet and esophageal endoscopic images was used to extract image features.Subsequently,K-nearest neighbors algorithm was used for classification based on the calculated Euclidean distance.The classification performance of FSL model was evaluated through the comparison with the original model and endoscopists.Results FSL model had a 4-class classification accuracy of 0.831,Macro AUC of 0.925,Macro F1-score of 0.831;moreover,the proposed model achieved diagnostic accuracies of 0.925 and 0.906 for CRLs and NETs,with F1 score of 0.850 and 0.805.Additionally,the proposed model exhibited high classification consistency(Kappa=0.775)and interpretability.Conclusion The established FSL model performs well in distinguishing CRLs,NETs,SLPs and traditional adenomas on endoscopic images,indicating its potential utility in assisting the identification of colorectal submucosal tumors under endoscopy.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from the biliary epithelial cells of the liver. Radical surgical resection remains the only potentially curative treatment but still with a dismal prognosis. In light of research progress in tumor immunotherapy, the combination of chemotherapy and immunotherapy has recently emerged as a first-line regimen for a significantly improved survival in patients with ICC. Genomics-based targeted therapy can benefit ICC patients with specific gene mutations. Additionally, systemic combined with local treatment can also benefit a group of patients with ICC. The management of ICC remains challenging and we hereby reviewed the treatment strategies of ICC to provide valuable references for clinical diagnosis, treatment, and basic research of ICC.

Objective:To evaluate the efficacy and safety of periarticular cocktail injection analgesia after arthroscopic rotator cuff repair surgery.Methods:From June 2020 to May 2021, 120 patients with rotator cuff tears were treated at Shandong University Qilu Hospital (Qingdao) with arthroscopic rotator cuff repair surgery. The cohort included 45 males and 75 females, aged 61.35±5.75 years (range 57-67 years), with 58 cases involving the left shoulder joint and 62 cases involving the right shoulder joint. Patients were randomly divided into a cocktail group (receiving periarticular injections of ropivacaine, morphine, adrenaline, and compound betamethasone) and an analgesic pump group (using an analgesic pump). Standardized protocols were used for perioperative and postoperative analgesia. The visual analog scale (VAS) of pain and shoulder joint range of motion were recorded on the day of surgery, the first and second postoperative days, the day of discharge, and at follow-up at 2 and 6 weeks. The postoperative demand for temporary analgesics (celecoxib), as well as adverse reactions to cocktail injections and analgesic pump applications were also recorded.Results:There were no statistically significant differences in age, gender, surgical time, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, preoperative VAS score, surgical time, postoperative hospital stay, rotator cuff tear area, and intraoperative anchor number between the two groups of patients ( P>0.05). Patients who received periarticular cocktail injections performed better in terms of postoperative VAS scores and functional recovery. Compared with the analgesic pump group, the temporary use of analgesics in the cocktail group was significantly reduced at 6, 12, and 24 hours after surgery. After 12 hours of surgery, the cocktail group received 3(3, 4) points and the analgesic pump group received 5(5, 6) points, with statistically significant differences ( Z=143.004, P=0.003); 18 hours after surgery, the VAS score in the cocktail group showed a rebound, rising to 4(3, 4) points, but still lower than 5(4, 5) points in the analgesic pump group. There was no significant difference in VAS scores between the cocktail group and the analgesic pump group at 24-48 hours after surgery ( P>0.05). The use of cocktail injections was associated with lower VAS scores at 12 hours post-surgery ( OR=4.125; 95% CI: 2.672, 4.328; P=0.015). There is no correlation between age, BM, ASA, pre-operative VAS, surgical time, rotator cuff tear size, number of anchor bolts used, and postoperative VAS score at 12 hours. Multivariate regression analysis of postoperative 24-hour VAS scores showed that no factors were associated with postoperative 24-hour VAS scores. Conclusion:Periarticular cocktail injection can significantly reduce the need for postoperative pain relief and improve patient satisfaction, without posing significant risks after arthroscopic rotator cuff repair surgery.

Objective:To evaluate the relationship between the mechanism by which aucubin improved attention deficit hyperactivity disorder (ADHD) induced by maternal exposure to S-ketamine and GABAergic neurons in the habenular nucleus of offspring mice.Methods:SPF healthy C57BL/6 wild-type pregnant mice were used in this study, and an ADHD model in offspring mice was established by intraperitoneally injecting S-ketamine in the middle and late pregnancy. Twenty-four offspring of pregnant mice exposed to S-ketamine were divided into 2 groups ( n=12 each) at 14 days after birth using a random number table method: ADHD + normal saline group (AN group) and ADHD + aucubin group (AA group). Twenty-four offspring of pregnant mice exposed to normal saline were divided into 2 groups ( n=12 each) at 14 days after birth by a random number table method: control + normal saline group (CN group) and control + aucubin group (CA group). Aucubin 40 mg/kg was intraperitoneally injected once a day for 7 consecutive days in CA group and AA group, and the equal volume of normal saline was given instead in CN group and AN group. At 14 days after birth, the 16-channel microfilament array electrode was placed in the habenular nucleus, and the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was recorded when the mice buried beads in the marble burying test. At 21 days after birth (after the end of peritoneal administration), the impulsive and stereotypical behaviors of offspring mice were evaluated by elevated zero maze and marble burying test, respectively, and then the expression of glutamate decarboxylase 2 (GAD2) in habenular nucleus was detected by the immunofluorescence method. Results:Compared with CN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly increased, the expression of GAD2 was down-regulated, the time spent in the open arm was prolonged, the number of entries into the open arm and the number of buried beads were increased in AN group ( P<0.05), and no statistically significant differences were found in the above indexes in CA group ( P>0.05). Compared with AN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly decreased, the expression of GAD2 was up-regulated, the time spent in the open arm was shortened, and the number of entries into the open arm and the number of buried beads were decreased in AA group ( P<0.05). Conclusions:The mechanism by which aucubin alleviates prenatal S-ketamine exposure-induced ADHD may be related to increasing the number of GABAergic neurons in the habenular nucleus of offspring mice.