Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Chronic heart failure （CHF） is the terminal stage of various heart diseases， with high morbidity， mortality， and hospitalization rate. According to the theory of collateral diseases， the core pathogenesis of CHF is blood stasis of collaterals， water retention and stagnation， and pathogen accumulation in collaterals. Accordingly， the treatment should focus on reinforcing healthy Qi to warm Yang， activating blood to dredge collaterals， and excreting water to alleviate edema. On this basis， Qili Qiangxin capsules （QLQX） are created. This prescription can effectively treat chronic heart failure. Modern studies have shown that QLQX contains a variety of pharmacological components such as flavonoids， alkaloids， terpenoids， phenylpropanoids， phenolic acids， and cardiac glycosides. QLQX can improve the cardiac function， inhibit myocardial fibrosis， improve hemodynamics， mitigate inflammation， reduce cardiomyocyte apoptosis， and regulate the nervous system， with mild adverse reactions. This study analyzed the etiology and pathogenesis of CHF based on the theory of collateral diseases， explored the relationship between the prescription and syndrome， and delved into the material basis and mechanism of QLQX in the treatment of CHF， aiming to provide reference for the clinical application and scientific research of QLQX.

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Summarize the nursing experience of 9 children with X-linked agammaglobulinemia who were first treated with subcutaneous infusion of human immunoglobulin in mainland China. Nursing points: there is no precedent in mainland China for high-dose subcutaneous infusion of human immunoglobulin, therefore, it is necessary to make sufficient preparation and care before infusion, pay attention to the observation and care of drug infusion, provide guidance on home medication, pay attention to psychological care, and ensure that patients smoothly transition from hospital medication to home medication. All 9 patients successfully completed subcutaneous injection of human immunoglobulin treatment, ensure smooth transition of patients from hospital medication to home medication. and no serious adverse reactions occurred, resulting in good results.

【Objective】 To investigate the clinical features and gene analysis of one pedigree with multiple endocrine neoplasia type 2A （MEN2A） so as to clarify the diagnosis and classification of the disease， guide treatment and prevention， and improve prognosis. 【Methods】 The clinical data of a 36-member MEN2A family， including 6 probands， with medullary thyroid carcinoma， were investigated， and the peripheral blood genomic DNA of 28 family members （blood sample of one proband was not collected） was extracted. PCR amplification was performed on exons 8， 10， 11， 13， 14， 15 and 16 of the RET gene， and the products were directly sequenced. 【Results】 Review of the medical history showed that two probands with medullary thyroid carcinoma were accompanied with hyperparathyroidism， and one family member had pheochromocytoma. The RET gene mutation test confirmed that 13 family members， consisting of 5 probands and 8 family members， had the RET proto-oncogene exon 10 missense mutation. The heterozygous missense had mutation c.1852T>A， leading to the conversion of cysteine （TGC） at position 618 to serine （AGC） （Cys618Ser）. All subjects carrying RET gene Cys618Ser mutation had abnormal thyroid ultrasound change， accompanied with elevated calcitonin levels. Subjects carrying wild type of RET gene had normal calcitonin levels. The family was finally diagnosed with MEN2A by RET gene detection. 【Conclusion】 RET gene detection plays key role in the diagnosis and treatment of patients with MEN2A family and has guiding value in the follow-up and prognosis of asymptomatic carriers. There is a positive correlation between calcitonin level and the RET protooncogene mutation Cys618Ser. Patients suspected of MEN2A should be screened in time.

Objective:To investigate the prognostic significance of D-dimer level in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 70 newly diagnosed DLBCL patients who were admitted to Tianjin People's Hospital from January 2015 to June 2019 were retrospectively analyzed. The optimal cut-off value of D-dimer for survival was determined according to the receiver operating characteristic (ROC) curve, and the patients were grouped. The differences of coagulation related indexes and clinicopathological features between patients with different D-dimer levels were compared. Kaplan-Meier method was used for univariate analysis of overall survival (OS), and Cox regression model was used for multivariate analysis of OS.Results:According to ROC curve, the best cut-off value of D-dimer for survival was 0.75 mg/L. The proportion of patients with different clinical staging, international prognostic index score, lactate dehydrogenase level had statistically significant differences between the D-dimer ≥0.75 mg/L group (36 cases) and <0.75 mg/L group (34 cases) (all P < 0.05). The prothrombin time of D-dimer ≥ 0.75 mg/L group and < 0.75 mg/L group were (13.5±0.9) s and (13.0±0.8) s, respectively, and the activated partial thromboplastin time were (37±5) s and (34±6) s, respectively,and the differences were statistically significant (all P < 0.05). Univariate analysis showed that the 5-year OS rates of DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ, international prognostic index score > 2, lactate dehydrogenase level > 240 U/L, B symptoms, D-dimer level ≥0.75 mg/L were decreased (all P < 0.05). Multivariate Cox regression analysis showed that D-dimer ≥0.75 mg/L was an independent risk factor for OS of DLBCL patients ( HR=0.368, 95% CI 0.144-0.944, P= 0.038). Conclusion:The level of D-dimer can be used as a clinical indicator to judge the prognosis of DLBCL patients, and the prognosis of patients with high D-dimer level is poor.

Objective: To investigate the characteristic and prognostic significance of leukemia stem cells associated antigens expressions including CD34, CD38, CD123, CD96 and TIM-3 in t (8;21) AML. Methods: Bone marrow samples of 47 t (8;21) AML patients were collected at diagnosis from October 2015 to April 2018 in Peking University Peoples’ Hospital, then flow cytometry method was performed to detect the expression frequencies of CD34, CD38, CD123, CD96 and TIM-3 to analyze the relationship between leukemia stem cells associated antigens expressions and relapse. Results: Of 47 t (8;21) AML patients tested, the median percentages of CD34⁺CD38^-, CD34⁺ CD38^-CD123⁺, CD34⁺CD38^- CD96⁺ and CD34⁺ CD38^- TIM-3⁺ cells among nucleated cells were 2.37%, 0.24%, 0.27% and 0.06%, respectively. All the frequencies of CD34⁺CD38^-, CD34⁺CD38^-CD123⁺, CD34⁺CD38^-CD96⁺ and CD34⁺ CD38^-TIM-3⁺ cells had no impact on the achievement of CR after the first course of induction. All higher frequencies of CD34⁺CD38^-, CD34⁺CD38^-CD123⁺, CD34⁺CD38^-CD96⁺ cells were related to higher 2-year CIR rate. Whereas, the frequency of CD34⁺ CD38^- TIM-3⁺ cells had no impact on CIR rate. Both high frequency of CD34⁺ CD38^- cells and the high level of minimal residual diseases (patients with <3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy) were independent poor prognostic factors of CIR[P=0.025, HR=6.9 (95%CI 1.3-37.4) ; P=0.031, HR=11.1 (95%CI 1.2-99.2) ]. Conclusion Different leukemia stem cells associated antigens had distinct prognostic significance in t (8;21) AML. High frequencies of CD34⁺ CD38^-, CD34⁺ CD38^- CD123⁺ and CD34⁺CD38^-CD96⁺ cells at diagnosis predicted relapse in patients with t (8;21) AML.

Objective: To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification. Methods: Cobalt chloride (CoCl₂) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC₅₀) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level. Results: The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)). Conclusion Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.

Objective: To investigate the prognostic value of prognostic nutritional index (PNI) in patients with diffuse large B-cell lym-phoma (DLBCL). Methods: We retrospectively reviewed the medical records of 82 patients with DLBCL treated at Tianjin Union Medi-cal Center between June 2010 and June 2016. The optimal cutoff value of PNI was determined using a receiver operating characteristic (ROC) curve and the Youden index. The relationship of high and low PNI with the clinical characteristics of the patients, therapeutic ef-ficacy, and prognosis were analyzed. Results: Overall, mean PNI of the patients was 46.17±8.8. When the PNI was 44.15, the Youden in-dex was found to be maximal, with a sensitivity of 74.6% and specificity of 67.2%. There were 38 patients (46.3%) in the low PNI group (<44.15) and 44 patients (53.7%) in the high PNI group (≥44.15). Data analysis showed that PNI was correlated with Eastern Coopera-tive Oncology Group performance status (ECOG PS), Ann Arbor stage, international prognostic index (IPI) score, and lactic acid dehydro-genase (LDH) level (P<0.05). The total effective rate of the low PNI group was significantly lower than that of the high PNI group (65.8% vs. 86.4%; χ2=4.848; P=0.028). The 3-year overall survival (OS) rate of the entire group of patients was 69.1%. The 1-, 2-, and 3-year OS rates of the low PNI group (86.8%, 67.8%, and 56.9%, respectively) were significantly lower than that of the high PNI group (96.7%, 89.5%, and 80.2%, respectively; χ2=9.421, P=0.002). Univariate analysis showed that PNI<44.15, ECOG PS≥2, IPI>2, stageⅢ/Ⅳ, and lymphocyte count<1.0×109/L had a significant impact on predicting OS (P<0.05). Multivariate analysis showed that PNI<44.15 (P=0.006) and stageⅢ/Ⅳ(P=0.011) were independent factors for predicting OS. Conclusions: PNI might be used as a simple and feasible clinical prognostic indicator in patients with DLBCL.

Atherosclerosis is the major cause of ischemic stroke.Given the importance of the early diagnosis and intervention of atherosclerotic plaques,the use of molecular imaging techniques for early diagnosis of atherosclerosis has become a research focus in recent years.This article reviews the advances in research on molecular imaging in the aspect of early diagnosis of atherosclerosis.