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.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Aberrant expression of Colgalt1 is closely associated with tumorigenesis and tumor progres-sion;however,the mechanism by which it regulates macrophages to influence tumor development remains poorly understood.This study aimed to establish a macrophage-specific Colgalt1 gene knockout mouse model to delve into the mechanisms through which Colgalt1 modulates macrophage function and subse-quently affects the occurrence and progression of tumor-related diseases.Initially,Colgalt1flox+mice were generated using gene editing techniques,followed by crossing with Lyz2-Cre+mice,which exhibit tissue-specific expression in the myeloid lineage(including monocytes and mature macrophages).Through this strategy,mice with the genotype Colgalt1-/-Lyz2-Cre+were successfully obtained,achieving conditional knockout of the Colgalt1 gene in macrophages.Colgalt1flox/flox Lyz2-Cre-mice were used as control.PCR and agarose gel electrophoresis were employed to identify the Flox and Cre genotypes of the knockout mice.RT-qPCR and Western Blot techniques were utilized to detect the expression levels of Colgalt1 in BMDMs from knockout mice at both the mRNA and protein levels,respectively.Western Blot results re-vealed a significant downregulation of Colgaltl expression in BMDMs from knockout mice compared to controls(P＜0.01).RT-qPCR results demonstrated a significant reduction in Colgalt1 mRNA levels in BMDMs from knockout mice compared to contro1s(P＜0.001),while no significant differences in Col-galt1 mRNA expression were observed in liver,lung,or spleen tissues between the two groups.Addition-ally,immunohistochemistry was employed to detect Colgalt1 expression in liver-specific macrophages,re-vealing an absence of Colgalt l-positive staining in liver macrophages from knockout mice.HE staining was used to observe cellular morphology in liver tissues from both groups of mice,showing no significant differences in cellular morphology or obvious pathological changes in tissues and organs.Moreover,the o-verall survival of the mice was not affected.Finally,RT-qPCR was used to assess the expression of mac-rophage-related inflammatory factors in BMDMs from both groups of mice.The results indicated that com-pared to controls,knockout mice exhibited downregulated expression of TNF-α(P＜0.05)and signifi-cantly upregulated expression of IL-10(P＜0.01),Arginase1(P＜0.001),and CD206(P＜0.001)in BMDMs,suggesting an anti-inflammatory trend and M2 polarization of macrophages following Colgalt 1 knockout.In summary,this study successfully established a macrophage-specific Colgalt1 gene knockout mouse model,providing a more reliable experimental animal model for in-depth exploration of the specific roles of Colgalt1 in macrophage functional regulation and the pathogenesis of tumor-related diseases.This model holds promise for identifying novel therapeutic targets and strategies for tumors and other diseases.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.

Aberrant expression of Colgalt1 is closely associated with tumorigenesis and tumor progres-sion;however,the mechanism by which it regulates macrophages to influence tumor development remains poorly understood.This study aimed to establish a macrophage-specific Colgalt1 gene knockout mouse model to delve into the mechanisms through which Colgalt1 modulates macrophage function and subse-quently affects the occurrence and progression of tumor-related diseases.Initially,Colgalt1flox+mice were generated using gene editing techniques,followed by crossing with Lyz2-Cre+mice,which exhibit tissue-specific expression in the myeloid lineage(including monocytes and mature macrophages).Through this strategy,mice with the genotype Colgalt1-/-Lyz2-Cre+were successfully obtained,achieving conditional knockout of the Colgalt1 gene in macrophages.Colgalt1flox/flox Lyz2-Cre-mice were used as control.PCR and agarose gel electrophoresis were employed to identify the Flox and Cre genotypes of the knockout mice.RT-qPCR and Western Blot techniques were utilized to detect the expression levels of Colgalt1 in BMDMs from knockout mice at both the mRNA and protein levels,respectively.Western Blot results re-vealed a significant downregulation of Colgaltl expression in BMDMs from knockout mice compared to controls(P＜0.01).RT-qPCR results demonstrated a significant reduction in Colgalt1 mRNA levels in BMDMs from knockout mice compared to contro1s(P＜0.001),while no significant differences in Col-galt1 mRNA expression were observed in liver,lung,or spleen tissues between the two groups.Addition-ally,immunohistochemistry was employed to detect Colgalt1 expression in liver-specific macrophages,re-vealing an absence of Colgalt l-positive staining in liver macrophages from knockout mice.HE staining was used to observe cellular morphology in liver tissues from both groups of mice,showing no significant differences in cellular morphology or obvious pathological changes in tissues and organs.Moreover,the o-verall survival of the mice was not affected.Finally,RT-qPCR was used to assess the expression of mac-rophage-related inflammatory factors in BMDMs from both groups of mice.The results indicated that com-pared to controls,knockout mice exhibited downregulated expression of TNF-α(P＜0.05)and signifi-cantly upregulated expression of IL-10(P＜0.01),Arginase1(P＜0.001),and CD206(P＜0.001)in BMDMs,suggesting an anti-inflammatory trend and M2 polarization of macrophages following Colgalt 1 knockout.In summary,this study successfully established a macrophage-specific Colgalt1 gene knockout mouse model,providing a more reliable experimental animal model for in-depth exploration of the specific roles of Colgalt1 in macrophage functional regulation and the pathogenesis of tumor-related diseases.This model holds promise for identifying novel therapeutic targets and strategies for tumors and other diseases.

OBJECTIVE: To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO). METHODS: Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement). RESULTS: All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L^-1 and (204.47±35.59) μg·L^-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L^-1 and (311.12±42.23) μg·L^-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s^-1, (0.57±0.15) m, and (0.99±0.11) m·s^-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s^-1, (0.50±0.14) m, and (0.95±0.09) m·s^-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05). CONCLUSION The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Tibia/physiopathology* ; Aged ; Biomechanical Phenomena ; Retrospective Studies ; Osteoarthritis, Knee/physiopathology*

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy