Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Traditional Chinese medicine (TCM) is an ancient medical system distinctive and effective in treating cancer, depression, coronavirus disease 2019 (COVID-19), and other diseases. However, the relatively abstract diagnostic methods of TCM lack objective measurement, and the complex mechanisms of action are difficult to comprehend, which hinders the application and internationalization of TCM. Recently, while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research, the rise of machine learning (ML) has significantly enhanced their integration with TCM. This article introduces representative methodological cases in quality control, mechanism research, diagnosis, and treatment processes of TCM, revealing the potential applications of ML technology in TCM. Furthermore, the challenges faced by ML in TCM applications are summarized, and future directions are discussed.

OBJECTIVE: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. METHODS: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. RESULTS: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. CONCLUSION At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.
Humans ; Femur Head/pathology* ; Osteonecrosis/therapy* ; Macrophages/pathology* ; Inflammation ; Femur Head Necrosis/pathology*

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Objebtive:To investigate the effect of baicalin on cell apoptosis and related cytokines in diabetic retinopathy.Methods:Sixty SD rats were randomly divided into a control group, a model group, and a baicalin group, with 20 rats in each group. The diabetic retinopathy model was established after fed by a high-sugar, high-fat diet for 4 weeks by intraperitoneal injection of 50 mg/kg streptozotocin. Rats in the control group weren’t done any treatment, only with normal diet. Rats in the model group was not given drug treatment,While rats in the baicalin group 50 mg/kg intrabitoneal injection of baicalin. The results of HE staining, TUNEL cell apoptosis, retinal cell apoptosis index, and the expression of cleaved-cysteinyl aspartate-specific proteinase-3 (cleaved-Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) protein in the retina of the three groups were observed.Results:The internal limiting membrane of the retina in the control group was smooth. Compared with the control group, the loss of ganglion cells in the model group was significantly increased, the retinal thickness was thinner, and the thickness of the inner nuclear layer and the outer nuclear layer was thinner. Compared with the model group, the number of ganglion cells in the baicalin group was significantly increased, the retinal thickness was thickened, and the thickness of the inner nuclear layer and the outer nuclear layer was thickened. Apoptotic cells were brown after TUNEL labeling. A large number of apoptotic cells were observed in the model group, and the cell arrangement was disordered. Only a few apoptotic cells were observed in the control group, and the cells were arranged neatly. Compared with the model group, the apoptotic cells in the baicalin group were significantly reduced ( P < 0.05), and the cells were arranged neatly. The apoptosis index of retinal cells in the sham group was lower than that in the model group and the baicalin group, and the baicalin group was lower than that in the model group ( P < 0.05). Compared with the control group, the expression of cleaved-Caspase-3 and Bax protein in the retina of the model group was significantly increased, and Bcl-2 was significantly decreased; the difference was statistically significant ( P < 0.05). Compared with the model group, the expression of cleaved-Caspase-3 and Bax protein in the baicalin group was down-regulated, and Bcl-2 was significantly up-regulated; the difference was statistically significant ( P < 0.05). Conclusions:Baicalin can improve diabetic retinopathy by inhibiting the apoptosis rate of DR rats, down-regulating the expression of cleaved-Caspase-3 and Bax, and up-regulating the expression of Bcl-2.

From January 1, 2013, to March 1, 2024, nine patients with hematological malignancies complicated by Gilbert’s syndrome in Peking University People’s Hospital underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients comprised seven male and two female cases, with a median age of 38 (13-60) years old. Among them, three cases were acute myeloid leukemia, three cases were acute lymphocytic leukemia, two cases were myelodysplastic syndrome, and one case was chronic myelomonocytic leukemia. None of the patients had viral hepatitis. Of the nine cases, seven cases received the Bu-Cy+ATG regimen, while the other two cases received the TBI-Cy+ATG regimen (Bu, busulfan; Cy, cyclophosphamide; ATG, antithymocyte immunoglobulin; and TBI, total body irradiation). All patients achieved neutrophil engraftment, and eight received platelet engraftment. The median total bilirubin level was 45.4 (22.5-71.2) μmol/L before transplantation and 22.0 (18.0-37.2) μmol/L on -1d of preconditioning. The total bilirubin level on +20d after the transplantation of eight patients decreased compared with the baseline level before transplantation. Moreover, one patient had a transient increase in the total bilirubin level on +5d after transplantation, which was considered to be attributed to the toxicity of Bu. No patients were complicated by hepatic veno-occlusive disease. The median follow-up time was 739 (42-2 491) days. During the follow-up period, one patient died of recurrence, and the remaining eight patients had disease-free survival events.

[摘 要] 目的：系统评估经动脉化疗栓塞（TACE）和酪氨酸激酶抑制剂（TKI）联合（TT）联合或不联合PD-1抗体（PD-1Ab）治疗晚期肝细胞癌（aHCC）的疗效与潜在不良反应（AE）。方法：检索PubMed、中国知网（CNKI）、Embase、Web of Science等数据库，时限为各数据库建库始至2024年1月31日。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用Stata16.0软件进行Meta分析。结果：纳入17项研究，共2 334例aHCC患者。Meta分析结果显示，与TT疗法相比，PD-1Ab的加入能显著改善aHCC患者的总生存期（OS）[HR = 0.44，95% CI（0.36，0.51），P < 0.000 01]和无进展生存期（PFS）[HR = 0.47，95% CI（0.42，0.52），P < 0.000 01]，同时提高aHCC患者的客观缓解率（ORR）[HR = 1.65，95% CI（1.46，1.86），P < 0.000 01]和疾病控制率（DCR）[HR = 1.26，95% CI（1.15，1.38），P < 0.000 01]；不同基线资料如ECOG-PS、肝外转移与否、BCLC分期、肿瘤大小、Child-Pugh评分及肝门静脉侵犯与否等aHCC患者均可从TT PD-1Ab疗法中获益；两治疗方案间全级别与 ≥3级AE的总发生率无显著差异，但高血压、甲状腺功能减退及反应性皮肤血管增生等症状在接受TT PD-1Ab治疗的患者中更为常见。结论：相较于TT疗法，PD-1Ab的加入可显著延长aHCC患者OS和PFS，并提高其整体ORR与DCR；TT PD-1Ab治疗组患者发生全级别及≥ 3级AE的整体发生率没有显著增加，整体耐受性良好，但在高血压、皮肤与黏膜及甲状腺AE上有较高的发生率，应予以重视。

Objective To assess the effect of ultrasonic thyroid artificial intelligence(AI)-assisted diagnostic system(AI-assisted diagnostic system)for diagnosing medullary thyroid carcinoma(MTC)compared with different physicians and taken papillary thyroid carcinoma(PTC)as the controls.Methods Totally 63 MTC,70 PTC and 62 benign thyroid nodules confirmed by pathology were enrolled.AI-assisted diagnostic system was utilized to analyze thyroid nodules and identify the likelihood of malignancy,and the probability value threshold was set at ≥0.40.All thyroid nodules were retrospectively reviewed and categorized by 3 physicians(1 senior physician,1 attending physician and 1 junior physician)according to Chinese thyroid imaging reporting and data system(C-TIRADS).The efficacy of AI-assisted diagnostic system and physicians for diagnosing MTC and PTC were evaluated.Results AI-assisted diagnostic system showed lower sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and area under the curve(AUC)for diagnosing MTC and PTC compared with physicians.Significant differences of AUC were found between senior physician and AI-assisted diagnostic system,as well as between attending physician and AI-assisted diagnostic system for diagnosing MTC and PTC(all P＜0.01),while no significant difference of AUC was between junior physicians and AI-assisted diagnostic system(both P＞0.05).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and AUC for AI-assisted diagnostic system for diagnosing MTC were all lower than those for diagnosing PTC,but the AUC was not significantly different(P＞0.05).Conclusion Ultrasonic thyroid AI-assisted diagnostic system had relatively high value for diagnosing MTC.