BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

Ovarian cancer （OC） is one of the most common malignant tumors in women， with the mortality rate being the highest among gynaecological malignant tumors. As the atypical symptoms of OC are difficult to be detected in the early stage， most patients are already in the advanced stage when being diagnosed. As a result， the clinical treatment has limited effects. Currently， the main therapies for OC are surgery and chemotherapy， while their drug resistance and adverse reactions seriously reduce the quality of life of patients. In recent years， traditional Chinese medicine （TCM） has attracted the attention of clinicians and researchers because of its high efficacy， low toxicity， and mild side effects. According to the TCM philosophy of treatment based on syndrome differentiation， the Chinese medicines with multiple targets， wide range， and mild side effects can be screened based on the molecular targets involved in the occurrence and development of OC， which can bring out the unique advantages of TCM in the treatment of OC. Modern studies have shown that the occurrence and development of OC are closely related to the abnormal expression of multiple signaling pathways. The continued abnormal activation of the signal transducer and activator of transcription 3 （STAT3） signaling pathway can lead to abnormal proliferation and malignancy of OC. cause abnormal proliferation and malignant transformation of OC， which is closely related to the development of OC. In addition， studies have shown that Chinese medicine can inhibit the proliferation， angiogenesis， invasion， and metastasis and promote the autophagy and apoptosis of OC cells by regulating the Janus kinase 2 （JAK2）/STAT3 signaling pathway， providing new therapeutic strategies and ideas for the prevention and treatment of OC. This paper summarizes the role of JAK2/STAT3 signaling pathway in OC development by reviewing the relevant articles and reviews the mechanism and research progress of active components and compound prescriptions of Chinese medicine intervening in OC development by regulating the JAK2/STAT3 signaling pathway. This review is expected to provide a systematic reference for clinical research and drug development of OC.

Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Diabetic retinopathy（DR）， as one of the most common and serious microvascular complications of diabetes mellitus， seriously threatens human health， and belongs to "Xiaoke eye diseases" in traditional Chinese medicine（TCM）， which has been richly experienced by medical practitioners through the ages， but is mostly recorded in a piecemeal manner and has not been systematically researched. This disease is featured by long course and repeated attack， and is refractory， which belongs to the research category of "persistent illness entering collaterals". Systematic establishment of TCM collateral disease theory for guiding prevention and treatment of DR has important clinical value. On the basis of close correlation between tertiary collaterals at the terminal of collaterals and capillaries and microcirculation， the concept of "tertiary collaterals-microvascular" is proposed. It is pointed out that DR falls within the scope of "tertiary collaterals-microvascular" diseases， and presents four types of micro-pathological characteristics， including stasis， insufficiency， growth and bleeding of tertiary collaterals. It is concluded that "deficiency of both Qi and Yin" is the basic pathogenesis of DR， and "blood stasis and collateral obstruction" is the important pathogenesis and key factor. Thus， the treatment method of "dispersing blood stasis， dredging collateral， tonifying Qi and Yin， stopping hemorrhage and improving eyesight" is determined， and the formula of Tongluo Mingmu capsules is developed. The article tightly focuses on the pathological changes such as stasis， growth， insufficiency and bleeding of collaterals， addresses both symptoms and root causes， and plays a synergistic role of both dispersing stasis and stopping bleeding. In this way， it can realize the purpose of tonifying Qi and Yin to replenish the essence， dispersing stasis and dredging collaterals to meet the requirement， as well as stopping hemorrhage and improving eyesight to deal with changes. Fundamental researches demonstrate that Tongluo Mingmu capsules has synergy effects of protecting both retinal capillaries and retinal cells. Phase-Ⅲ clinical trial of new drug has proven definite clinical efficacy and good safety， which provides a new drug choice for enhancing clinical effect of DR， and further supports the scientific value of Luobing theory in preventing and treating DR and other clinically significant diseases.

Didangtang is a classic formula for treating blood stasis and heat， as recorded in the Treatise on Febrile Diseases， and it has been highly praised by medical practitioners throughout history. It has been recorded in many traditional Chinese medical texts and used to this day. This article comprehensively examined the records of Didangtang in different ancient versions of Treatise on Febrile Diseases by excavating and sorting out related ancient medical books and modern literature. It also investigated the dosage unit measurement， preparation method， and content of the formula in medical books throughout history. The article provided a detailed summary and exploration of the origins and processing methods of rhubarb， peach kernels， leeches， and flies in the formula. At the same time， it reviewed the clinical practice of Didangtang by medical practitioners throughout history in relevant medical books， mainly including the adjustment of dosage forms， the increase or decrease in medicinal taste and dosage， the expansion of clinical application， and the creation and elucidation of similar formulas. Although there may be differences in the above information among medical practitioners throughout history， the basic idea of attacking blood stasis and heat is consistent. In addition， based on clinical practice， the author adhered to the principle of treating stasis and heat disease as the first reference when using Didangtang. It was suggested that blood should be circulated instead of stopping in the treatment of stasis and heat accumulation syndrome. At the same time， it was believed that the use of the method of attacking stasis and heat to regulate brain diseases and mental illnesses derives from the fact that removing stasis and generating new energy can nourish the heart and mind， providing ideas for the treatment of such diseases with Didangtang. On this basis， modern clinical and animal experiments have shown that Didangtang has certain effects in improving microcirculation disorders， regulating blood rheology and hemodynamics， enhancing insulin resistance， and inhibiting inflammatory reactions. This may be an important mechanism for the formula to ''conquer blood stasis and heat''. This article explored the textual research and clinical mechanism of Didangtang， presenting facts and evidence， so as to provide a reference for the clinical application of Didangtang and the research on other prescriptions.

Guided by Academician Zhang Boli's theory of "dampness， turbidity， phlegm， and fluid-related diseases"，this paper elaborated on the pathogenesis and syndrome differentiation treatment of heart failure from the perspective of the "spleen-mitochondria". It analyzed the essential similarities between "spleen-mitochondria" and "dampness， turbidity， phlegm， and fluid-related diseases"， as well as their close association with the onset of heart failure. Furthermore，it explored the connection between spleen function and mitochondrial function in traditional Chinese medicine （TCM），positing that the spleen's role in transportation and transformation is analogous to mitochondrial material metabolism and energy conversion，with spleen deficiency closely related to mitochondrial dysfunction. It thus concluded that mitochondrial material metabolism and energy conversion represent the microscopic essence of the spleen's role in transportation and transformation，and mitochondrial dysfunction is a contributing factor to pathological products like dampness and turbid phlegm，which are closely associated with the occurrence of heart failure. The four elements of dampness，turbidity，phlegm，and fluid are a series of related symptoms resulting from abnormal fluid transportation and transformation，serving as both factors in the onset of heart failure and the core pathological basis for its deterioration. Therefore，during the treatment of heart failure，it is essential to regulate mitochondrial function. Early intervention should focus on eliminating dampness and turbidity to improve mitochondrial function and restore normal energy metabolism. In the middle and late stages，emphasis should be placed on resolving phlegm，promoting blood circulation，warming Yang，and reducing water retention to alleviate mitochondrial damage and improve cardiac function. Supporting Qi and strengthening the spleen should be a continuous approach，and treatment should be adjusted to enhance mitochondrial function and stabilize the condition，thereby improving prognosis. This paper discussed the role of the spleen and mitochondria in the pathogenesis of heart failure，examined the evolution of heart failure mechanisms from the perspective of dampness， turbidity， phlegm， and fluid-related diseases，and proposed a phased treatment strategy. It enriched the theory of dampness， turbidity， phlegm， and fluid-related diseases and offered new strategies for heart failure treatment. However，in practical application，TCM strategies for treating heart failure need to be integrated with modern medical approaches to provide a more solid scientific foundation for treatment.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

AIM:To compare the effect of AT TORBI 709M and Tecnis ZMT intraocular lenses on astigmatism correction in patients with corneal astigmatism at 3 mo after operation based on the standard astigmatism vector analysis.METHODS: This was a retrospective case-control study. The clinical data of 69 patients(69 eyes)with corneal astigmatism who underwent phacoemulsification and implantation of toric intraocular lens(IOL)from June 2021 to December 2021 in Day Surgery Center of Xi'an No.1 Hospital was analyzed. The patients were divided into two groups. In group one, 38 cases(38 eyes)were implanted with AT TORBI 709M, and 31 patients(31 eyes)with Tecnis ZMT in group two. The axial length, preoperative astigmatism and axis, and the degree of intraocular lens were recorded. The uncorrected distance visual acuity(UCDVA), best corrected distance visual acuity(BCDVA), diopter, residual astigmatism and axis were recorded preoperatively and at 1 wk, 1 and 3 mo postoperatively. The postoperative surgical indicators, including spherical equivalent(SE), target induced astigmatism vector(TIA), surgically induced astigmatism vector(SIA), magnitude of error(ME), absolute value of angle of error(|AE|), absolute value of difference vector(|DV|), correction index(CI), and index of success(IOS)were evaluated by the standard astigmatism vector analysis.RESULTS:Postoperative UCDVA and BCDVA were significantly improved(all P<0.001), and there were statistically significant differences compared to preoperative UCDVA and BCDVA(all P<0.001). While, there was no significant difference in UCDVA and BCDVA between the two groups(P=0.275, 0.124). The standard astigmatism vector analysis showed that a good astigmatism correction was achieved in both AT TORBI 709M group and Tecnis ZMT group, and both |DV| and IOS were close to 0(P=0.329, 0.288). The CI of the AT TORBI 709M group was closer to 1, indicating a better astigmatism correction, while the CI of the Tecnis ZMT group was higher than 1, suggesting an overcorrection of astigmatism. However, the difference between the two groups was not statistically significant(P=0.193). The mean residual astigmatism at 3 mo postoperatively was -0.11±0.91 D in the AT TORBI 709M group and -0.46±0.76 D in the Tecnis ZMT group, respectively, showing no statistically significance difference(t=1.732, P=0.088).CONCLUSION:Both the flat loop AT TORBI 709M and the double C-loop Tecnis ZMT intraocular lenses can effectively improve postoperative visual acuity in patients with regular corneal astigmatism, showing good rotational stability and comparable correction abilities for both astigmatism with the rule and against-the-rule astigmatism.

[Objective] To establish a cryopreservation protocol for small-volume (≤1 mL) red blood cells (RBCs) and to evaluate the reactivity and stability of blood group antigens after cryopreservation, so as to explore its potential application in immunohematology reference laboratories. [Methods] Small-volume RBCs were cryopreserved for 120 days, followed by thawing and deglycerolization to restore the RBC components. The quality of the RBCs was assessed. Serum antibodies were serially diluted and reacted with RBCs before and after cryopreservation, and agglutination scores were recorded to quantitatively evaluate the reactivity and stability of blood group antigens such as Rh, Duffy, Lewis, Kidd, M, and H. Flow cytometry was used to analyze the percentage and mean fluorescence intensity of ABO antigen expression on RBCs before and after cryopreservation to assess the usability of cryopreserved RBCs in flow immunophenotyping and blood group subtype studies. [Results] The hemolysis rate of thawed and deglycerolized RBCs was (0.27±0.10)%, with a supernatant free hemoglobin level of (0.52±0.14) g/L, and the RBC recovery rate was (69.12±7.91)%. The direct antiglobulin test (DAT) was negative for all thawed RBCs. There was no difference in the reactivity of blood group antigens before and after cryopreservation, and no difference in the percentage and mean fluorescence intensity of A and B antigen expression on RBCs before and after cryopreservation. [Conclusion] The small-volume RBC cryopreservation protocol can be applied to immunohematology analysis in reference laboratories and is expected to be widely used in blood group identification, antibody screening, identification, and blood group-related research.