Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Objective:To explore the optimization potential of clinical target volume (CTV) delineation proposed in the guidelines of the Oncology Group (RTOG), the Francophone Group of Urological Radiotherapy (GFRU), and the European Society for Radiotherapy and Oncology (ESTRO) based on prostate bed local occurrence patterns after radical prostatectomy identified using prostate-specific membrane antigen positron emission tomography (PSMA PET).Methods:A retrospective analysis was conducted on patients with local prostate bed recurrence after radical prostatectomy who underwent PSMA PET at the Department of Nuclear Medicine, Peking University First Hospital from September 2021 to February 2024. The central point of each recurrence was marked. A six-zone method was established based on prostate bed anatomy and the characteristics of cross-sectional imaging. Then, the positional relationships (within or outside) were recorded with respect to recurrences and CTV defined by the RTOG, GFRU, and ESTRO (CTV RTOG, CTV GFRU, and CTV ESTRO), followed the analysis of the recurrence rates and distribution characteristics of various zones. Results:A total of 63 patients with prostate bed recurrence after radical prostatectomy were enrolled in this study, including 97 recurrences. The recurrence rates in the six zones were as follows: 10% of zone 1, 22% of zone 2, 29% of zone 3, 2% of zone 4, 12% of zone 5a, 18% of zone 5b, and 7% of zone 6. Among these zones, zones 2 and 3 showed the highest and second-highest recurrence rates, respectively. CTV GFRU and CTV ESTRO completely covered zones 2 and 3, while CTV RTOG covered zone 2 completely and zone 3 partially. Zone 4, characterized by a low recurrence rate, was not covered by CTV GFRU and CTV ESTRO but was entirely covered by CTV RTOG. Zone 5a, with a recurrence rate of 12%, was completely covered by CTV RTOG but was partially covered by CTV GFRU and CTV ESTRO. The range of 1.3 cm in front of the posterior wall of the bladder covered all recurrences in zone 5a. Conclusions:For CTV delineation of the prostate cancer surgical bed, zone 4, the anterior half of the bladder above the pubic symphysis midpoint, should be contracted due to the low recurrence rate in this zone. In contrast, the anterior boundary above the pubic symphysis midpoint should extend to 1.3 cm in front of the posterior wall of the bladder to completely cover the recurrence zones.

Objective:To investigate the correlation between pathological features at the positive margins and biochemical re-currence after radical prostatectomy for prostate cancer.Methods:From June 2014 to December 2019,a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching(1:1).One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study.All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0.BCR-free survival was estimated using the Kaplan-Meier method.An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis(CART).Cox proportional hazards regression model was used to assess the association between variables and BCR-free surviv-al.Results:A total of 200 patients were included in this study,and 177 patients with pT2 stage were pathological after operation.The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months.A total of 28 cases of biochemi-cal recurrence were found through PSA follow-up after surgery,including 6 cases(6.0％)in the negative margin group and 22 cases(22.0％)in the positive margin group.The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group(log rank x2=9.336,P=0.003).It was found that the length of positive margin≥1 mm in the positive margin group was positively correlated with postoperative biochemical re-currence.Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of pos-itive ≥ 1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin.Conclusion:The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.

Objective:To explore the optimization potential of clinical target volume (CTV) delineation proposed in the guidelines of the Oncology Group (RTOG), the Francophone Group of Urological Radiotherapy (GFRU), and the European Society for Radiotherapy and Oncology (ESTRO) based on prostate bed local occurrence patterns after radical prostatectomy identified using prostate-specific membrane antigen positron emission tomography (PSMA PET).Methods:A retrospective analysis was conducted on patients with local prostate bed recurrence after radical prostatectomy who underwent PSMA PET at the Department of Nuclear Medicine, Peking University First Hospital from September 2021 to February 2024. The central point of each recurrence was marked. A six-zone method was established based on prostate bed anatomy and the characteristics of cross-sectional imaging. Then, the positional relationships (within or outside) were recorded with respect to recurrences and CTV defined by the RTOG, GFRU, and ESTRO (CTV RTOG, CTV GFRU, and CTV ESTRO), followed the analysis of the recurrence rates and distribution characteristics of various zones. Results:A total of 63 patients with prostate bed recurrence after radical prostatectomy were enrolled in this study, including 97 recurrences. The recurrence rates in the six zones were as follows: 10% of zone 1, 22% of zone 2, 29% of zone 3, 2% of zone 4, 12% of zone 5a, 18% of zone 5b, and 7% of zone 6. Among these zones, zones 2 and 3 showed the highest and second-highest recurrence rates, respectively. CTV GFRU and CTV ESTRO completely covered zones 2 and 3, while CTV RTOG covered zone 2 completely and zone 3 partially. Zone 4, characterized by a low recurrence rate, was not covered by CTV GFRU and CTV ESTRO but was entirely covered by CTV RTOG. Zone 5a, with a recurrence rate of 12%, was completely covered by CTV RTOG but was partially covered by CTV GFRU and CTV ESTRO. The range of 1.3 cm in front of the posterior wall of the bladder covered all recurrences in zone 5a. Conclusions:For CTV delineation of the prostate cancer surgical bed, zone 4, the anterior half of the bladder above the pubic symphysis midpoint, should be contracted due to the low recurrence rate in this zone. In contrast, the anterior boundary above the pubic symphysis midpoint should extend to 1.3 cm in front of the posterior wall of the bladder to completely cover the recurrence zones.

Aim To evaluate the effectiveness and safety of remimazolam tosylate for administering general anesthesia in morbidly obese patients.Methods This clinical trial was conducted at a single center from De-cember 2021 to October 2023.It assessed 108 morbid-ly obese patients(body mass index,BMI≥40)who underwent laparoscopic sleeve gastrectomy.Patients were randomly assigned to either the remimazaolam group(Group R)or the propofol group(Group P)for general anesthesia induction and maintenance.The primary outcome was to compare the incidence of ad-verse events and postoperative recovery characteristics between the two groups.Results During induction pe-riod,the incidence of adverse events was higher in group P,including hypotension(P＜0.01),hypox-emia(P＜0.05),bradycardia(P＜0.01),and in-creased vasopressor requirement(P＜0.05).The time to loss of consciousness and BIS falling to 60 was shor-ter in group P than in group R(P＜0.01).There were no statistically significant differences between the two groups in terms of postoperative quality of recovery(QoR-40 score),24-hour postoperative pain visual an-alogue scale(VAS)scores and morphine consump-tion.In conclusion,remimazolam tosylate,utilized for anesthesia induction in morbidly obese patients,signif-icantly reduced hypotension and hypoxemia compared to propofol,while it could also maintain similar postop-erative recovery quality.Conclusions Remimazolam is effective in reducing the incidence of hypotension and hypoxaemia during the induction period of general anaesthesia in morbidly obese patients and it is compa-rable to propofol in terms of quality of postoperative re-covery.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVES: To study the effect of breastfeeding on immune function in infants with human cytomegalovirus (HCMV) infection. METHODS: A retrospective analysis was performed on the medical data of 135 infants with HCMV infection who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2021 to May 2022, and all these infants received breastfeeding. According to the results of breast milk HCMV-DNA testing, the infants were divided into two groups: breast milk HCMV positive (n=78) and breast milk HCMV negative (n=57). According to the median breast milk HCMV-DNA load, the infants in the breast milk HCMV positive group were further divided into two subgroups: high viral load and low viral load (n=39 each). Related indicators were compared between the breast milk positive and negative HCMV groups and between the breast milk high viral load and low viral load subgroups, including the percentages of peripheral blood lymphocyte subsets (CD3⁺ T cells, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, and CD19⁺ B cells), CD4⁺/CD8⁺ ratio, IgG, IgM, IgA, and urine HCMV-DNA load. RESULTS: There were no significant differences in the percentages of CD3⁺ T cells, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, and CD19⁺ B cells, CD4⁺/CD8⁺ ratio, IgG, IgM, IgA, and urine HCMV-DNA load between the breast milk HCMV positive and HCMV negative groups, as well as between the breast milk high viral load and low viral load subgroups (P>0.05). CONCLUSIONS Breastfeeding with HCMV does not affect the immune function of infants with HCMV infection.
Female ; Child ; Humans ; Infant ; Breast Feeding ; Cytomegalovirus Infections ; CD8-Positive T-Lymphocytes ; Retrospective Studies ; Infectious Disease Transmission, Vertical ; Milk, Human ; Cytomegalovirus ; Immunity ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M

AIM To establish an UPLC-MS/MS method for the simultaneous content determination of chlorogenic acid,umbellifolactone,rutin,isochlorogenic acid A and isochlorogenic acid C in Artemisia sieversiana Ehrhart ex Willd.and Ajania tenuifolia(Jacquem.ex DC.)Tzvelev in Schischk.&Bobrov by HPLC,and compare the differences between them.METHODS The analysis of 50%methanol extract of both was performed on a 30℃thermostatic CAPCELL PAK-C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of acetonitrile-0.2%phosphoric acid water,flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 290 nm.A t-test was used to compare the contents differences of five constituents in the two crude drugs.RESULTS Five constituents showed good linear relationships within their own ranges(r≥0.999 5),whose average recoveries were 96.03%-103.11%,with the RSDs of 0.51%-2.26%.The average contents of chlorogenic acid,umbellifolactone,rutin,isochlorogenic acid A and isochlorogenic acid C in A.sieversiana and A.tenuifolia were 3.61,0.71,1.46,8.74,1.44 mg/g and 2.60,0.26,0.79,6.31,1.22 mg/g,respectively.CONCLUSION The method is accurate,reliable and reproducible.There was no significant difference in the five chemical constituents between A.sieversiana and A.tenuifolia.

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

OBJECTIVE: To explore the effects and molecular mechanism of circ-SFMBT2 on the proliferation, migration and invasion of acute myeloid leukemia (AML) cells. METHODS: Bone marrow samples from 35 pediatric AML patients and 35 healthy controls in Henan Provincial Children's Hospital from April 2015 to April 2017 and human bone marrow stromal cell lines (HS-5) and AML cell lines (HL-60, THP-1, U-937 and Kasumi-1) were collected. The expressions of circ-SFMBT2, miR-491-5p and homeobox A9 (HOXA9) in bone marrow samples and cells were detected by RT-qPCR and Western blot. The Pearson method was used to analyze the correlation of circ-SFMBT2, miR-491-5p and HOXA9 mRNA expression levels in bone marrow samples of AML patients. HL-60 cells were cultured in vitro and divided into 5 groups: Control, si-NC, si-circ-SFMBT2, si-circ-SFMBT2+anti-NC and si-circ-SFMBT2+anti-miR-491-5p, HL-60 cells were transfected with si-NC, si-circ-SFMBT2, anti-NC, and miR-491-5p inhibitor with Lipofectamine™ 3000. RT-qPCR and Western blot were performed to detect the expression levels of circ-SFMBT2, miR-491-5p and HOXA9 in cells of each group. The proliferation activity of HL-60 cells in each group was detected by CCK-8 assay at 24, 48 and 72 h after transfection, respectively. The apoptosis rate was detected by flow cytometry. The migration and invasion abilities of cells were detected by Transwell assay. The regulatory roles of circ-SFMBT2, miR-491-5p and HOXA9 in AML cells were verified by dual-luciferase reporter gene assay, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) experiments. RESULTS: The expression levels of circ-SFMBT2 and HOXA9 mRNA were increased in bone marrow samples and cell lines (HL-60, THP-1, U-937 and Kasumi-1) of children with AML (P <0.001), while the expression level of miR-491-5p was significantly decreased (P <0.001). Pearson correlation analysis showed that the expression levels of circ-SFMBT2 and miR-491-5p in bone marrow samples of AML children were negatively correlated (r =-0.905), miR-491-5p was also negatively correlated with HOXA9 mRNA (r =-0.930), while the expression levels of HOXA9 mRNA and circ-SFMBT2 was positively correlated (r =0.911). The overall survival rate of AML children with high expression of circ-SFMBT2 was significantly decreased than those with low expression of circ-SFMBT2 (P <0.05). Silencing of circ-SFMBT2 could greatly up-regulate the expression of miR-491-5p, decrease the expression of HOXA9, inhibit the proliferation, migration and invasion of AML cells, and promote cell apoptosis (P <0.05). Down-regulation of miR-491-5p expression greatly attenuated the inhibitory effects of circ-SFMBT2 silencing on cell proliferation, migration and invasion (P <0.05). Dual-luciferase reporter gene assay, RNA pull-down and RIP experiments confirmed that circ-SFMBT2 could target miR-491-5p and negatively regulate the expression of miR-491-5p in AML, and HOXA9 was the target of miR-491-5p. CONCLUSION Silencing of circ-SFMBT2 may inhibit the proliferation, migration and invasion of AML cells by regulating the miR-491-5p/HOXA9 axis.
Child ; Humans ; Cell Line, Tumor ; Cell Proliferation ; Genes, Homeobox ; HL-60 Cells ; Leukemia, Myeloid, Acute ; Luciferases ; MicroRNAs ; Repressor Proteins ; RNA, Messenger ; RNA, Circular/genetics*