Exosomes are small vesicles with a lipid bilayer membrane structure that have applied in precision medicine due to their non-invasive nature， high accessibility， and stability. Exosomes play a crucial role in processes such as tumor metastasis， invasion， and angiogenesis. Gynecological malignancies primarily include cervical cancer， ovarian cancer， and endometrial cancer， and their early diagnosis and treatment have long been a focus of research. As novel biological markers， exosomes exhibit high specificity and can effectively block the occurrence and progression of gynecological malignancies. This article explores the diagnostic and therapeutic applications of exosomes in cervical cancer， ovarian cancer， and endometrial cancer in detail. In cervical cancer， exosomes are involved in processes such as HPV infection， angiogenesis， and immune evasion， with specific miRNAs （such as miR-30d-5p and let-7d-3p） serving as diagnostic markers. Furthermore， exosomes can act as targeted drug delivery vehicles and vaccine development platforms. In ovarian cancer， the miRNAs carried by exosomes （such as miR-21 and the miR-200 family） have reference value for early diagnosis， and exosomes play an important role in chemotherapy resistance and tumor progression. For endometrial cancer， miRNAs in exosomes （such as miR-15a-5p and miR-106b-5p） can serve as biomarkers for early detection. Additionally， this article highlights the challenges faced by exosomes in clinical applications， such as the complexity of isolation and extraction and the identification of cell sources， and emphasizes the necessity for further basic research and clinical trials. This study provides new ideas and methods for the early diagnosis and precision treatment of gynecological malignancies， holding significant theoretical and clinical importance.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

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*

ObjectiveTo explore the effects of exosomal CXCL on the biological behavior of cervical cancer cells and its underlying mechanisms. MethodsChemokine CXCL was first screened through bioinformatics databases. The GEPIA database was analyze CXCL expression in cervical cancer tissues and adjacent normal cervical tissues. Western blot was performed to detect CXCL expression levels in cervical cancer cells （Caski） and normal cervical epithelial cells （H8）. The successful isolation of exosomes was confirmed by nanoparticle tracking analysis， transmission electron microscopy （TEM） and Western blot. ELISA was employed to detect the expression level of exosomes CXCL was determined by ELISA. After CXCL knockdown via siRNA transfection， cells were divided into three groups： blank control， negative control and experimental groups. Cell proliferation was evaluated using the CCK-8 assay， while cell migration and invasion were assessed by Transwell assays. ResultsExosomal CXCL expression was significantly upregulated in cervical cancer cells compared with normal cervical epithelial cells （P<0. 01）， and also markedly elevated in cervical cancer tissues compared with adjacent normal tissues. After low expression of CXCL knockdown significantly reduced CXCL expression in both cancer cells and their derived exosomes（P<0. 05）. Low expression markedly inhibited the proliferation， invasion and migration abilities ConclusionSilencing exosomal CXCL may inhibit the malignant biological behavior of cancer cells.

Objective To systematically retrieve,evaluate and summarize the related evidences of plate-let implantation delayed management in the patients with allogeneic hematopoietic stem cell transplantation.Methods According to the"6S"model,the clinical decision systems,guidelines network,professional associa-tion websites and databases were retrieved to collect the evidences regarding the platelet implantation delayed management in the patients with allogeneic hematopoietic stem cell transplantation,the retrieval time limit was from the database establishment to May 2024.Two researchers independently conducted the quality eval-uation of the literatures,evidence extraction and evidence integration.Results A total of 17 articles were fi-nally included,including 1 guideline,2 clinical decisions,3 systematic reviews,5 expert consensus and 6 ran-domized controlled trials.A total of 24 pieces of evidences were summarized in 5 aspects,including the pre-transplantation evaluation and prevention,application of mesenchymal stem cells,thrombopoietic drugs man-agement,blood transfusion support and complication management such as bleeding.Conclusion The medical and care staffs should carry out the best evidence practice for platelet implantation delayed management in the patients with allogeneic hematopoietic stem cell transplantation by combining with the domestic clinical situa-tion to reduce the hemorrhage in multiple organ systems after transplantation and improve the survival quality.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

AIM: To explore the clinicopathological and immunohistochemistry(IHC)characteristics of meibomian gland carcinoma(MGC).METHODS: Patients who were pathologically diagnosed as MGC from January 1, 2015 to December 31, 2020 in our hospital were enrolled, and their clinicopathological information was retrospectively analyzed. Cancer tissues from all the cases were IHC stained. En Vision two-step method, DAB staining, as well as hematoxylin re-staining were applied in the IHC assay.RESULTS: A total of 50 patients with 21 males and 29 females(1:1.38)were enrolled in the study, ranging from 26 to 80 years old, with a median age of 60 years. The upper eyelid, which was the predilection site, accounting for 66%(33/50). Histopathologically, moderately or poorly differentiated was in the majority(35/50, 70%). The expression rates of IHC parameters of MGC patients were as follows: GATA-3(49/50, 98%), EMA(49/50, 98%), CAM5.2(42/50, 84%), AR(41/50, 82%), MSH2(50/50, 100%), MSH6(50/50, 100%), MLH1(50/50, 100%), PMS2(50/50, 100%), Ki67(positive, 50%-90%). All the patients were followed up for 12 to 72 mo, with 5 cases of recurrence and 0 deaths.CONCLUSION: Pathological diagnosis of MGC should focus on observing cancer cells' cytoplasm to find relevant clues for cortical gland differentiation. Comprehensive analysis of multiple indicators is required when using IHC to assist diagnosis. For most MGC cancer cells, positive expressions of GATA-3, EMA, AR, CAM5.2 and a high Ki67 proliferation index could be always found. In addition, screening for Muir-Torre syndrome related IHC indicators could be also performed in diagnosing MGC simultaneously.

OBJECTIVE To establish a determination method for the related substances of LPM3480392, a novel Gi protein-biased opioid receptor(MOR) agonist. METHODS The separation was carried out with Waters Symmetry Shield RP18 (150 mm×4.6 mm, 3.5 μm) by gradient elution method, using a mixture of 0.002 5 mol·L–1 sodium 1-octanesulfonate monohydrate in 0.01 mol·L–1 potassium dihydrogen phosphate-water solution(containing 0.1% triethylamine, adjusted pH to 2.50 with phosphate acid) and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min–1 and the UV detection wavelength was set at 210 nm. RESULTS The chromatographic peaks of LPM3480392 and impurity A, impurity B, impurity C, impurity E and impurity F could be completely separated, the linear relationship of LPM3480392 was good in 0.064 9−5.191 2 μg·mL–1, while impurity A, impurity B, impurity C, impurity E and impurity F showed good linear relationship within 0.066 6−7.610 4 μg·mL–1, 0.166 0−3.794 0 μg·mL–1, 0.209 2−4.463 2 μg·mL–1, 0.167 9−7.672 6 μg·mL–1 and 0.016 4−7.505 7 μg·mL–1, respectively. The recovery rate was within 93.0%−103.2%. CONCLUSION The method is suitable for the determination of related substances in LPM3480392, and can provide valuable reference for the follow-up research and development of LPM3480392.

ObjectiveThe natural history of chronic HBV infection often involves a histologically defined immune tolerance state， and once such immune tolerance state is broken， antiviral therapy should be initiated immediately. This study aims to investigate the correlation between immune-mediated liver injury and virological indicators for HBV and precisely identify the patients with a histologically defined immune tolerance state. MethodsThis study was conducted among 577 HBeAg-positive chronic hepatitis B （CHB） patients with HBV DNA >2×10⁶ IU/mL who did not receive antiviral therapy in The Fifth Medical Center of PLA General Hospital， Tianjin Second People’s Hospital， Shanghai Ruijin Hospital， and Taizhou Hospital of Zhejiang Province from January 2010 to December 2022. Liver biopsy was performed to determine the extent of liver injury， and the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and virological indicators were measured. The proportion of patients with a histologically defined immune tolerance state was analyzed based on the cut-off values of noninvasive indicators recommended in various guidelines， especially HBV load. In addition， a diagnostic model was established for the histologically defined immune tolerance state based on serum HBV DNA at the time when its correlation with liver immunopathological injury disappeared as the new threshold in combination with multiple indicators. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. The binary Logistic regression analysis was used to establish a multivariate diagnostic model； the area under the receiver operating characteristic curve （AUC） was used to investigate the diagnostic efficiency of different models， and the Z test was used for comparison of AUC. ResultsAmong the patients with an immune tolerance state defined by the noninvasive indicators in the Chinese guidelines （2022 edition）， the EASL guidelines （2017 edition）， the AASLD guidelines （2018 edition）， and the APASL guidelines （2015 edition） for the prevention and treatment of CHB， the patients with a histologically defined immune tolerance state who met the definition in this article （HBV DNA>2×10⁶ IU/mL） accounted for 47.0%， 38.5%， 36.0%， and 44.6%， respectively， which did not exceed 50%. When the threshold of serum HBV DNA increased to >2×10⁸ IU/mL， although the correlation between immune-mediated liver injury and HBV DNA disappeared （r=-0.029， P=0.704）， the patients with a histologically defined immune tolerance state reached only 52.0%. In the cohort of 251 HBeAg-positive patients with serum HBV DNA >1×10⁸ IU/mL， there were significant differences in the levels of HBsAg， HBeAg， HBV DNA， ALT， and AST between the significant liver injury group with 140 children and the non-significant liver injury group with 111 patients （all P<0.05）， and the multivariate binary Logistic regression analysis showed that AST， HBV DNA， and HBeAg were influencing factors for histologically defined immune tolerance state in patients （all P<0.05）. Based on the above indicators and related clinical data， a predictive model was established as logit（P）=1.424－0.028×AST， with an AUC of 0.730， an optimal cut-off value of 30.5 U/L， a sensitivity of 52.8%， and a specificity of 84.1%. A total of 238 adult patients with chronic HBV infection who underwent liver biopsy in Taizhou Hospital of Zhejiang Province were enrolled as the validation cohort， and the analysis showed that the predictive model established in this study had a better efficiency than AST/ALT， FIB-4， and APRI， with an AUC of 0.698， 0.555， 0.518， and 0.373， respectively （all P<0.05）. ConclusionFor HBeAg-positive patients with chronic HBV infection and HBV DNA>2×10⁸ IU/mL， an AST level of >30.5 U/L might indicate the “breakdown” of histologically defined immune tolerance state.

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.