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 compare the efficacy of percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar fractures. METHODS: A retrospective case-control study was used to analyze the clinical data of 78 patients with osteoporotic thoracic and lumbar fractures admitted from October 2017 to May 2019. According to the surgical method, it was divided into percutaneous pedicle screw combined with unilateral nail placement combined with unilateral bone cement strengthening group(bone cement group) and percutaneous pedicle screw combined with bilateral nail placement(screw group). In the bone cement group, 40 patients included 16 males and 24 females, with a mean age of (62.1±8.1) years old. In the screw group, 38 patients included 18 males and 20 females with a mean age of (65.1±9.3) years old. The operation time, intraoperative blood loss, length of hospital stay and postoperative complications were compared between two groups. The kyphosis Cobb angle, anterior edge height ratio, central height ratio and pain visual analogue score(VAS) were compared. RESULTS: All patients were followed up for 25 to 36 months. The operation time (70.1±17.3) min of the cement group was shorter than that of the screw group (78.6±18.2) min(P<0.05). There were no significant differences in intraoperative blood loss and length of hospital stay(P>0.05). The VAS in the cement group 1 year 1.5±0.5 and the latest follow-up 0.5±0.3 after operation were lower than 1 year 1.8±0.3 and the latest follow-up 0.8±0.4 in the screw group(P<0.05). The kyphosis Cobb angle, anterior edge height ratio, central height ratio in bone cement group, 1 year (6.2±1.2)°, (86.6±3.5)%, (91.1±2.5)%, the last follow-up (6.4±0.7)°, (85.5±3.3)%, (90.5±6.3)% were better than that of the screw group 1 year (6.8±1.4)°, (83.1±2.4)%, (89.9±3.4)% and the latest follow-up (7.1±1.1)°, (82.6±4.1)%, (87.6±5.9)%(P<0.05). There were 3 cases of bone cement leakage in the cement group, all of which had no clinical symptoms;and 2 cases of pedicle screws were extracted in the screw group, and the screws were removed at the last follow-up. CONCLUSION Percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar compression fractures in the elderly can achieve satisfactory efficacy and effectively relieve the pain of patients, but the former internal fixation system is more stable, and the long-term follow-up can effectively maintain the height of the anterior middle column and the correction of kyphosis deformity, and the incidence of chronic low back pain is lower.
Humans ; Male ; Female ; Aged ; Bone Cements ; Middle Aged ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Case-Control Studies ; Bone Nails ; Pedicle Screws

OBJECTIVE: To compare clinical effects of external fixation and minimally invasive percutaneous plate osteosynthesis (MIPPO) after external fixation in treating open fractures of tibial shaft. METHODS: From January 2020 to June 2022, 151 patients with open fracture of tibial shaft treated with external fixation stenting were divided into external fixation group and combined group according to different surgical methods. There were 81 patients in external fixation group, including 48 males and 33 females, aged from 21 to 68 years old with an average of (42.58±7.44) years old;according to Gustilo classification, 49 patients with typeⅡ, 32 patients with type ⅢA;the time from injury to treatment ranged from 2.5 to 10 h with an average of (4.25±0.74) h;external fixed stenting was performed. There were 70 patients in combined group, including 42 males and 28 females, aged from 20 to 69 years old with an average of (41.39±7.02) years old;35 patients with type Ⅱ and 35 patients with type ⅢA according to Gustilo classification;the time from injury to treatment ranged from 3 to 9 h with an average of (4.31±0.85) h;MIPPO treatment was performed after external fixed stenting. The time of callus formation, fracture healing and complications were compared between two groups. Rasmussen score and Hospital for Special Surgery (HSS) score were used to evaluate functional recovery of knee joint at 6 months after operation. RESULTS: Both groups were followed up for 6 to 13 months with an average of (10.17±2.33) months. The time of callus formation and fracture healing were (13.98±4.02) d and (70.26±12.15) d in combined group, and (18.56±4.37) d and (79.87±15.41) d in external fixation group, respectively. Combined group was better than external fixation group in the time of callus formation and fracture healing (P<0.05). At six months after operation, Rasmussen and HSS scores in combined group were (26.79±3.11) and (83.36±9.44), which were higher than those in external fixation group (24.51±4.63) and (79.63±8.46) (P<0.05). In external fixation group, there were 2 patients with incision infection, 2 patients with nail tract infection, 1 patient with stent loosening, fracture displacement, delayed union and malunion, and 1 patient with biocompatibility reaction in combined group, with statistical significance between two groups (P<0.05). CONCLUSION MIPPO could accelerate callus formation and fracture healing, improve knee function, improve clinical effects and reduce complications in patients with open tibial shaft fractures after external and external fixation.
Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Bone Plates ; External Fixators ; Fractures, Open/physiopathology* ; Stents ; Young Adult

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective:To explore the risk factors for recurrence of intussusception in children after successful ultrasound-guided saline enema reduction.Methods:The clinical and follow up data of 355 hospitalized children with intussusception at the First Affiliated Hospital of Zhengzhou University from Feb 2018 to Feb 2023 were reviewed.Patients were divided into two groups by recurrence develped and the differences were compared, Data with significant differences were incorporated into multi-factor logistic analysis.Results:The overall recurrence rate was 15.8% (56/355). By univariate variable analysis model, there were statistically significant differences between the two groups in age, previous intussusception history, vomiting, maximum diameter of concentric circles shown by ultrasound, and concurrent bowel organic diseases (lead points) (all P<0.05). In multivariate Logistic regression model, age, previous intussusception history, maximum diameter of concentric circles, and lead points were independent risk factors for recurrent intussusception after saline enema.The optimal cut-off values for age and maximum diameter of concentric circles were 2 years and 33.5 mm, respectively, according to ROC curve analysis. Conclusion:Age older than 2 years, previous intussusception history, maximum diameter of concentric circles longer than 33.5 mm, and lead points are independent risk factors for recurrence after saline enema.

Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.

Hepatocellular carcinoma(HCC)has become the second leading cause of cancer-related death worldwide,ranking 6th among all tumors.Due to the lack of obvious early symptoms,most patients are diagnosed in the advanced stage,and the clinical benefits of surgical resection and hepatic artery chemoembolization and radiofrequency ablation are very limited.In recent years,the advent of immune-targeted therapies has revolutionized the systemic and systemic treatment of patients with advanced HCC,however,there is a lack of strong clinical evidence on the safety and efficacy of immune and targeted therapies for special populations,including patients with human immunodeficiency virus(HIV)infection,active autoimmune disease,decompensated cirrhosis(Child B or C),patients with diabetes-associated metabolic syndrome,patients with portal hypertension,vascular invasion,or portal vein thrombosis(PVT),and patients with liver transplantation(LT).This article reviews the current research progress of immune and targeted drugs in special populations.

Background Sleep quality is one of the important factors affecting soldiers’ task performance. Objective To explore the effects of mindful attention awareness, burnout, and occupational stress on sleep quality among soldiers in plateau areas. Methods A total of 1090 soldiers were selected from four units in plateau areas by cluster sampling method and were asked to participate a cross-sectional questionnaire survey using the Pittsburgh Sleep Quality Index (PQSI), Occupational Stress Inventory (OSI), Maslach Burnout Inventory-General Survey (MBI-GS), and Mindful Attention Awareness Scale (MAAS). Correlation analysis, regression analysis, and mediated effect test were conducted for the study. Results Of the 1090 soldiers recruited, 1082 soldiers returned valid questionnaires, and the valid recovery rate was 99.26%. The median (P₂₅, P₇₅) score of PSQI was 4.00 (2.00,7.00), the median score of OSI was 26.00 (17.00, 34.00), the median score of MBI-GS was 3.53 (3.13, 4.00), and the median score of MAAS was 71.00 (59.00, 82.00). The burnout and mindful attention awareness levels varied among military personnel of different age groups (P<0.05), so did the burnout and occupational stress levels among military personnel of different length of service groups (P<0.05), and the occupational stress, PSQI, burnout, and mindful attention awareness levels among military personnel with different educational backgrounds and genders (P<0.05). The results of mediated effect test showed that occupational stress and burnout had both a parallel mediated effect and a sequential mediating effect on the relationship between mindful attention awareness and sleep quality, with effect sizes of 15.3%, 21.5% and 31.8%, respectively. Conclusion There is a mediated effect on the relationship between mindful attention awareness and sleep quality by the occupational stress and burnout of military personnel in plateau areas, and sleep quality is also affected by mindful attention awareness through the chain-mediated effect of occupational stress and burnout.